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16 pages, 2526 KiB

Open AccessArticle

Immobilization of Wnt Fragment Peptides on Magnetic Nanoparticles or Synthetic Surfaces Regulate Wnt Signaling Kinetics

by Bin Hu, Michael Rotherham, Neil Farrow, Paul Roach, Jon Dobson and Alicia J. El Haj

Int. J. Mol. Sci. 2022, 23(17), 10164; https://doi.org/10.3390/ijms231710164 - 5 Sep 2022

Cited by 5 | Viewed by 2075

Abstract

Wnt signaling plays an important role in embryogenesis and adult stem cell homeostasis. Its diminished activation is implicated in osteoporosis and degenerative neural diseases. However, systematic administration of Wnt-signaling agonists carries risk, as aberrantly activated Wnt/β-catenin signaling is linked to cancer. Therefore, technologies [...] Read more.

Wnt signaling plays an important role in embryogenesis and adult stem cell homeostasis. Its diminished activation is implicated in osteoporosis and degenerative neural diseases. However, systematic administration of Wnt-signaling agonists carries risk, as aberrantly activated Wnt/β-catenin signaling is linked to cancer. Therefore, technologies for local modulation and control of Wnt signaling targeted to specific sites of disease or degeneration have potential therapeutic value in the treatment of degenerative diseases. We reported a facile approach to locally activate the canonical Wnt signaling cascade using nanomagnetic actuation or ligand immobilized platforms. Using a human embryonic kidney (HEK293) Luc-TCF/LEF reporter cell line, we demonstrated that targeting the cell membrane Wnt receptor, Frizzled 2, with peptide-tagged magnetic nanoparticles (MNPs) triggered canonical Wnt signaling transduction when exposed to a high-gradient, time-varying magnetic field, and the induced TCF/LEF signal transduction was shown to be avidity-dependent. We also demonstrated that the peptide retained signaling activity after functionalization onto glass surfaces, providing a versatile platform for drug discovery or recreation of the cell niche. In conclusion, these results showed that peptide-mediated Wnt signaling kinetics depended not only on ligand concentration but also on the presentation method of the ligand, which may be further modulated by magnetic actuation. This has important implications when designing future therapeutic platforms involving Wnt mimetics. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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20 pages, 7106 KiB

Open AccessArticle

Anti-Inflammatory Fibronectin-AgNP for Regulation of Biological Performance and Endothelial Differentiation Ability of Mesenchymal Stem Cells

by Huey-Shan Hung, Kai-Bo Chang, Cheng-Ming Tang, Tian-Ren Ku, Mei-Lang Kung, Alex Yang-Hao Yu, Chiung-Chyi Shen, Yi-Chin Yang, Hsien-Hsu Hsieh and Shan-hui Hsu

Int. J. Mol. Sci. 2021, 22(17), 9262; https://doi.org/10.3390/ijms22179262 - 26 Aug 2021

Cited by 8 | Viewed by 3443 | Correction

Abstract

The engineering of vascular regeneration still involves barriers that need to be conquered. In the current study, a novel nanocomposite comprising of fibronectin (denoted as FN) and a small amount of silver nanoparticles (AgNP, ~15.1, ~30.2 or ~75.5 ppm) was developed and its [...] Read more.

The engineering of vascular regeneration still involves barriers that need to be conquered. In the current study, a novel nanocomposite comprising of fibronectin (denoted as FN) and a small amount of silver nanoparticles (AgNP, ~15.1, ~30.2 or ~75.5 ppm) was developed and its biological function and biocompatibility in Wharton’s jelly-derived mesenchymal stem cells (MSCs) and rat models was investigated. The surface morphology as well as chemical composition for pure FN and the FN-AgNP nanocomposites incorporating various amounts of AgNP were firstly characterized by atomic force microscopy (AFM), UV-Visible spectroscopy (UV-Vis), and Fourier-transform infrared spectroscopy (FTIR). Among the nanocomposites, FN-AgNP with 30.2 ppm silver nanoparticles demonstrated the best biocompatibility as assessed through intracellular ROS production, proliferation of MSCs, and monocytes activation. The expression levels of pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6, were also examined. FN-AgNP 30.2 ppm significantly inhibited pro-inflammatory cytokine expression compared to other materials, indicating superior performance of anti-immune response. Mechanistically, FN-AgNP 30.2 ppm significantly induced greater expression of vascular endothelial growth factor (VEGF) and stromal-cell derived factor-1 alpha (SDF-1α) and promoted the migration of MSCs through matrix metalloproteinase (MMP) signaling pathway. Besides, in vitro and in vivo studies indicated that FN-AgNP 30.2 ppm stimulated greater protein expressions of CD31 and von Willebrand Factor (vWF) as well as facilitated better endothelialization capacity than other materials. Furthermore, the histological tissue examination revealed the lowest capsule formation and collagen deposition in rat subcutaneous implantation of FN-AgNP 30.2 ppm. In conclusion, FN-AgNP nanocomposites may facilitate the migration and proliferation of MSCs, induce endothelial cell differentiation, and attenuate immune response. These finding also suggests that FN-AgNP may be a potential anti-inflammatory surface modification strategy for vascular biomaterials. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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10 pages, 2980 KiB

Open AccessArticle

One Pot Synthesis of Large Gold Nanoparticles with Triple Functional Ferrocene Ligands

by Shenqing Wang, Fang Liu, Yin Liu, Hongyu Zhou and Bing Yan

Int. J. Mol. Sci. 2021, 22(5), 2328; https://doi.org/10.3390/ijms22052328 - 26 Feb 2021

Cited by 3 | Viewed by 2863

Abstract

In biomedical, toxicological, and optoelectronic applications, the size of nanoparticles is one of the decisive factors. Therefore, synthesis of nanoparticles with controlled sizes is required. The current methods for synthesis of larger gold nanoparticles (GNPs, ~200 nm) are complex and tedious, producing nanoparticles [...] Read more.

In biomedical, toxicological, and optoelectronic applications, the size of nanoparticles is one of the decisive factors. Therefore, synthesis of nanoparticles with controlled sizes is required. The current methods for synthesis of larger gold nanoparticles (GNPs, ~200 nm) are complex and tedious, producing nanoparticles with a lower yield and more irregular shapes. Using ferrocene as a primary reducing agent and stabilizer, sodium citrate as a dispersant, and sodium borohydride as an accessory reducing agent, GNPs of 200 nm were synthesized in a one pot reaction. Besides the roles of reducing agent and GNP stabilizer, ferrocene also served a role of quantitative marker for ligand loading, allowing an accurate determinate of surface ligands. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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12 pages, 4420 KiB

Open AccessArticle

Boosting of Antibacterial Performance of Cellulose Based Paper Sheet via TiO₂ Nanoparticles

by Klaudia Maślana, Anna Żywicka, Karolina Wenelska and Ewa Mijowska

Int. J. Mol. Sci. 2021, 22(3), 1451; https://doi.org/10.3390/ijms22031451 - 1 Feb 2021

Cited by 13 | Viewed by 2765

Abstract

Here, we aimed to boost antibacterial performance of cellulose fibers for paper sheet application. Therefore, TiO₂ nanoparticles have been used with controlled loading onto the surface of the fibers. A simple and facile composite preparation route based on ultrasound and mechanical assisted [...] Read more.

Here, we aimed to boost antibacterial performance of cellulose fibers for paper sheet application. Therefore, TiO₂ nanoparticles have been used with controlled loading onto the surface of the fibers. A simple and facile composite preparation route based on ultrasound and mechanical assisted stirring has been developed. We tested cellulose paper enriched by TiO₂ from 1.0 wt% to 8.0 wt%, respectively. Antibacterial performance has been studied against Staphylococcus aureus and Escherichia coli bacteria. Studies showed that all composites exhibit significant capability to reduce living cells of S. aureus and E. coli bacteria at least 60%. The simplicity, low cost, and reproducibility of the prepared method indicates the potential to be scaled up for industrial applications. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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11 pages, 976 KiB

Open AccessArticle

Looking for the LOAEL or NOAEL Concentration of Nickel-Oxide Nanoparticles in a Long-Term Inhalation Exposure of Rats

by Boris A. Katsnelson, Ivan N. Chernyshov, Svetlana N. Solovyeva, Ilzira A. Minigalieva, Vladimir B. Gurvich, Irene E. Valamina, Oleg H. Makeyev, Renata R. Sahautdinova, Larisa I. Privalova, Anastasia E. Tsaregorodtseva, Artem V. Korotkov, Eugene A. Shuman, Vladimir G. Panov and Marina P. Sutunkova

Int. J. Mol. Sci. 2021, 22(1), 416; https://doi.org/10.3390/ijms22010416 - 3 Jan 2021

Cited by 6 | Viewed by 2634

Abstract

Rats were exposed to nickel oxide nano-aerosol at a concentration of 2.4 ± 0.4 µg/m³ in a “nose only” inhalation setup for 4 h at a time, 5 times a week, during an overall period of 2 weeks to 6 months. Based [...] Read more.

Rats were exposed to nickel oxide nano-aerosol at a concentration of 2.4 ± 0.4 µg/m³ in a “nose only” inhalation setup for 4 h at a time, 5 times a week, during an overall period of 2 weeks to 6 months. Based on the majority of the effects assessed, this kind of exposure may be considered as close to LOAEL (lowest observed adverse effect level), or even to NOAEL (no observed adverse effect level). At the same time, the experiment revealed genotoxic and allergic effects as early as in the first weeks of exposure, suggesting that these effects may have no threshold at all. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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14 pages, 4988 KiB

Open AccessArticle

Indocyanine Green Loaded Modified Mesoporous Silica Nanoparticles as an Effective Photothermal Nanoplatform

by Yiyu Wang, Chunqing Niu, Sisi Fan, Yuwei Li, Xiang Li, Yujun Dai, Jian Shi and Xinyu Wang

Int. J. Mol. Sci. 2020, 21(13), 4789; https://doi.org/10.3390/ijms21134789 - 6 Jul 2020

Cited by 18 | Viewed by 3851

Abstract

Photothermal therapy possesses great advantages for the treatment of drug-resistant tumors. Herein, Near Infrared (NIR)-triggered photothermal nanoparticles were developed through loading indocyanine green (ICG), a kind of NIR dye, into amino group-modified silica nanoparticles (SiO₂-NH₂ NPs). SiO₂-NH₂ [...] Read more.

Photothermal therapy possesses great advantages for the treatment of drug-resistant tumors. Herein, Near Infrared (NIR)-triggered photothermal nanoparticles were developed through loading indocyanine green (ICG), a kind of NIR dye, into amino group-modified silica nanoparticles (SiO₂-NH₂ NPs). SiO₂-NH₂ NPs were prepared with immobilization of the amino groups into the framework of silica nanoparticles (SiO₂ NPs) by employing (3-aminopropyl)-triethoxysilane (APTES). Before and after the modification of the amino group, the particle sizes of SiO₂ NPs showed similar value, around 100 nm. ICG was further adsorbed into SiO₂-NH₂ NPs by electrostatic attraction to enable SiO₂-NH₂@ICG NPs as a kind of photothermal agent. The loading rate of ICG to SiO₂-NH₂ was greatly increased compared to unmodified SiO₂, and the stability of ICG was also improved. Moreover, the SiO₂-NH₂@ICG NPs exhibited efficient photothermal effects due to ICG transforming laser power into local heat through the connected ICG, when NIR laser irradiation turned on for a couple of minutes. Finally, the in vitro antitumor efficacy of SiO₂-NH₂@ICG NPs was investigated by recording cell proliferation rate and further chronicled the apoptotic morphology evidence by a Calcein-AM/PI fluorescent staining assay, indicating the efficient photothermal targeted therapy for the HepG2 tumor cells. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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13 pages, 4295 KiB

Open AccessArticle

Combination with l-Menthol Enhances Transdermal Penetration of Indomethacin Solid Nanoparticles

by Noriaki Nagai, Fumihiko Ogata, Mizuki Yamaguchi, Yuya Fukuoka, Hiroko Otake, Yosuke Nakazawa and Naohito Kawasaki

Int. J. Mol. Sci. 2019, 20(15), 3644; https://doi.org/10.3390/ijms20153644 - 25 Jul 2019

Cited by 18 | Viewed by 4836

Abstract

This study designed the transdermal formulations containing indomethacin (IMC)—1% IMC was crushed with 0.5% methylcellulose and 5% 2-hydroxypropyl-β-cyclodextrin by the bead mill method, and the milled IMC was gelled with or without 2% l-menthol (a permeation enhancer) by Carbopol^® 934 (without menthol, [...] Read more.

This study designed the transdermal formulations containing indomethacin (IMC)—1% IMC was crushed with 0.5% methylcellulose and 5% 2-hydroxypropyl-β-cyclodextrin by the bead mill method, and the milled IMC was gelled with or without 2% l-menthol (a permeation enhancer) by Carbopol^® 934 (without menthol, N-IMC gel; with menthol, N-IMC/MT gel). In addition, the drug release, skin penetration and percutaneous absorption of the N-IMC/MT gel were investigated. The particle sizes of N-IMC gel were approximately 50–200 nm, and the combination with l-menthol did not affect the particle characterization of the transdermal formulations. In an in vitro experiment using a Franz diffusion cell, the skin penetration in N-IMC/MT gel was enhanced than the N-IMC gel, and the percutaneous absorption (AUC) from the N-IMC/MT gel was 2-fold higher than the N-IMC gel. On the other hand, the skin penetration from the N-IMC/MT gel was remarkably attenuated at a 4 °C condition, a temperature that inhibits all energy-dependent endocytosis. In conclusion, this study designed transdermal formulations containing IMC solid nanoparticles and l-menthol, and found that the combination with l-menthol enhanced the skin penetration of the IMC solid nanoparticles. In addition, the energy-dependency of the skin penetration of IMC solid nanoparticles was demonstrated. These findings suggest the utility of a transdermal drug delivery system to provide the easy application of solid nanoparticles (SNPs). Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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22 pages, 8488 KiB

Open AccessArticle

Transformation of Construction Cement to a Self-Healing Hybrid Binder

by Werner E.G. Müller, Emad Tolba, Shunfeng Wang, Qiang Li, Meik Neufurth, Maximilian Ackermann, Rafael Muñoz-Espí, Heinz C. Schröder and Xiaohong Wang

Int. J. Mol. Sci. 2019, 20(12), 2948; https://doi.org/10.3390/ijms20122948 - 17 Jun 2019

Cited by 3 | Viewed by 4529

Abstract

A new biomimetic strategy to im prove the self-healing properties of Portland cement is presented that is based on the application of the biogenic inorganic polymer polyphosphate (polyP), which is used as a cement admixture. The data show that synthetic linear polyp, with [...] Read more.

A new biomimetic strategy to im prove the self-healing properties of Portland cement is presented that is based on the application of the biogenic inorganic polymer polyphosphate (polyP), which is used as a cement admixture. The data show that synthetic linear polyp, with an average chain length of 40, as well as natural long-chain polyP isolated from soil bacteria, has the ability to support self-healing of this construction material. Furthermore, polyP, used as a water-soluble Na-salt, is subject to Na⁺/Ca²⁺ exchange by the Ca²⁺ from the cement, resulting in the formation of a water-rich coacervate when added to the cement surface, especially to the surface of bacteria-containing cement/concrete samples. The addition of polyP in low concentrations (<1% on weight basis for the solids) not only accelerated the hardening of cement/concrete but also the healing of microcracks present in the material. The results suggest that long-chain polyP is a promising additive that increases the self-healing capacity of cement by mimicking a bacteria-mediated natural mechanism. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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24 pages, 6099 KiB

Open AccessArticle

Toxic Effects of Low-Level Long-Term Inhalation Exposures of Rats to Nickel Oxide Nanoparticles

by Marina P. Sutunkova, Svetlana N. Solovyeva, Ilzira A. Minigalieva, Vladimir B. Gurvich, Irene E. Valamina, Oleg H. Makeyev, Vladimir Ya. Shur, Ekaterina V. Shishkina, Ilya V. Zubarev, Renata R. Saatkhudinova, Svetlana V. Klinova, Anastasia E. Tsaregorodtseva, Artem V. Korotkov, Eugene A. Shuman, Larisa I. Privalova and Boris A. Katsnelson

Int. J. Mol. Sci. 2019, 20(7), 1778; https://doi.org/10.3390/ijms20071778 - 10 Apr 2019

Cited by 36 | Viewed by 4745

Abstract

Rats were exposed to nickel oxide nanoparticles (NiO-NP) inhalation at 0.23 ± 0.01 mg/m³ for 4 h a day 5 times a week for up to 10 months. The rat organism responded to this impact with changes in cytological and some biochemical [...] Read more.

Rats were exposed to nickel oxide nanoparticles (NiO-NP) inhalation at 0.23 ± 0.01 mg/m³ for 4 h a day 5 times a week for up to 10 months. The rat organism responded to this impact with changes in cytological and some biochemical characteristics of the bronchoalveolar lavage fluid along with a paradoxically little pronounced pulmonary pathology associated with a rather low chronic retention of nanoparticles in the lungs. There were various manifestations of systemic toxicity, including damage to the liver and kidneys; a likely allergic syndrome as indicated by some cytological signs; transient stimulation of erythropoiesis; and penetration of nickel into the brain from the nasal mucous membrane along the olfactory pathway. Against a picture of mild to moderate chronic toxicity of nickel, its in vivo genotoxic effect assessed by the degree of DNA fragmentation in nucleated blood cells (the RAPD test) was pronounced, tending to increasing with the length of the exposure period. When rats were given orally, in parallel with the toxic exposure, a set of innocuous substances with differing mechanisms of expected bioprotective action, the genotoxic effect of NiO-NPs was found to be substantially attenuated. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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12 pages, 2763 KiB

Open AccessArticle

Toxicological Evaluation of SiO₂ Nanoparticles by Zebrafish Embryo Toxicity Test

by Sandra Vranic, Yasuhito Shimada, Sahoko Ichihara, Masayuki Kimata, Wenting Wu, Toshio Tanaka, Sonja Boland, Lang Tran and Gaku Ichihara

Int. J. Mol. Sci. 2019, 20(4), 882; https://doi.org/10.3390/ijms20040882 - 18 Feb 2019

Cited by 57 | Viewed by 8237

Abstract

As the use of nanoparticles (NPs) is increasing, the potential toxicity and behavior of NPs in living systems need to be better understood. Our goal was to evaluate the developmental toxicity and bio-distribution of two different sizes of fluorescently-labeled SiO₂ NPs, 25 [...] Read more.

As the use of nanoparticles (NPs) is increasing, the potential toxicity and behavior of NPs in living systems need to be better understood. Our goal was to evaluate the developmental toxicity and bio-distribution of two different sizes of fluorescently-labeled SiO₂ NPs, 25 and 115 nm, with neutral surface charge or with different surface functionalization, rendering them positively or negatively charged, in order to predict the effect of NPs in humans. We performed a zebrafish embryo toxicity test (ZFET) by exposing the embryos to SiO₂ NPs starting from six hours post fertilization (hpf). Survival rate, hatching time, and gross morphological changes were assessed at 12, 24, 36, 48, 60, and 72 hpf. We evaluated the effect of NPs on angiogenesis by counting the number of sub-intestinal vessels between the second and seventh intersegmental vessels and gene expression analysis of vascular endothelial growth factor (VEGF) and VEGF receptors at 72 hpf. SiO₂ NPs did not show any adverse effects on survival rate, hatching time, gross morphology, or physiological angiogenesis. We found that SiO₂ NPs were trapped by the chorion up until to the hatching stage. After chemical removal of the chorion (dechorionation), positively surface-charged SiO₂ NPs (25 nm) significantly reduced the survival rate of the fish compared to the control group. These results indicate that zebrafish chorion acts as a physical barrier against SiO₂ NPs, and removing the chorions in ZFET might be necessary for evaluation of toxicity of NPs. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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17 pages, 3905 KiB

Open AccessArticle

Imaging of Metastatic Cancer Cells in Sentinel Lymph Nodes using Affibody Probes and Possibility of a Theranostic Approach

by Makoto Tsuchimochi, Haruka Yamaguchi, Kazuhide Hayama, Yasuo Okada, Tomoyuki Kawase, Takamasa Suzuki, Norio Tsubokawa, Noriaki Wada, Atsushi Ochiai, Satoshi Fujii and Hirofumi Fujii

Int. J. Mol. Sci. 2019, 20(2), 427; https://doi.org/10.3390/ijms20020427 - 19 Jan 2019

Cited by 9 | Viewed by 6004

Abstract

The accurate detection of lymph node metastases is essential for treatment success in early-stage malignant cancer. Sentinel lymph node (SLN) biopsy is the most effective procedure for detecting small or micrometastases that are undetectable by conventional imaging modalities. To demonstrate a new approach [...] Read more.

The accurate detection of lymph node metastases is essential for treatment success in early-stage malignant cancer. Sentinel lymph node (SLN) biopsy is the most effective procedure for detecting small or micrometastases that are undetectable by conventional imaging modalities. To demonstrate a new approach for developing a more efficient SLN biopsy procedure, we reported a two-stage imaging method combining lymphoscintigraphy and near-infrared (NIR) fluorescence imaging to depict metastatic cancer cells in SLNs in vivo. Furthermore, the theranostic potential of the combined procedure was examined by cell culture and xenograft mouse model. Anti-HER2 and anti-epidermal growth factor receptor (EGFR) affibody probes were used for NIR fluorescence imaging. Strong NIR fluorescence signal intensity of the anti-EGFR affibody probe was observed in SAS cells (EGFR positive). Radioactivity in the SLNs was clearly observed in the in vivo studies. High anti-EGFR affibody NIR fluorescence intensity was observed in the metastatic lymph nodes in mice. The addition of the IR700-conjugated anti-EGFR affibody to the culture medium decreased the proliferation of SAS cells. Decreased proliferation was shown in Ki-67 immunohistochemistry in xenograft tumors. Our data suggest that a two-stage combined imaging method using lymphoscintigraphy and affibody probes may offer the direct visualization of metastatic lymph nodes as an easily applied technique in SLN biopsy. Although further animal studies are required to assess the effect of treating lymphatic metastasis in this approach, our study results provide a foundation for the further development of this promising imaging and treatment strategy for earlier lymph node metastasis detection and treatment. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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15 pages, 3767 KiB

Open AccessArticle

Protein Food Matrix–ZnO Nanoparticle Interactions Affect Protein Conformation, but May not Be Biological Responses

by Song-Hwa Bae, Jin Yu, Tae Geol Lee and Soo-Jin Choi

Int. J. Mol. Sci. 2018, 19(12), 3926; https://doi.org/10.3390/ijms19123926 - 7 Dec 2018

Cited by 28 | Viewed by 4380

Abstract

Because of their nutritional value, zinc oxide (ZnO) nanoparticles (NPs) are applied as a dietary source of zinc, by direct addition to complex, multiple-component food matrices. The thereby occurring interactions of NPs with food matrices may have biological or toxic effects. In particular, [...] Read more.

Because of their nutritional value, zinc oxide (ZnO) nanoparticles (NPs) are applied as a dietary source of zinc, by direct addition to complex, multiple-component food matrices. The thereby occurring interactions of NPs with food matrices may have biological or toxic effects. In particular, NP interactions with food protein can lead to structural deformation of the latter, potentially changing its digestive efficiency and gastrointestinal absorption. In this study, interactions between ZnO NPs and a representative complex protein food matrix, skim milk, were compared with those between NPs and individual components of this food matrix (i.e., protein, saccharide, and mineral). The effects of the interactions on biological responses were investigated in terms of cytotoxicity, cellular uptake, intestinal transport, structural deformation for proteins, and digestive efficiency. The results demonstrated that the physicochemical properties of ZnO NPs were strongly influenced by the protein matrix type, leading to an increased dispersion stability in the complex protein matrix. However, these interactions did not affect cell proliferation, membrane damage, cellular uptake, intestinal transportation, or protein digestive efficiency, although a slight conformational change of proteins was observed in the presence of ZnO NPs. In conclusion, no toxic effects were observed, suggesting the safety of NPs when added to complex food matrices. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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13 pages, 3400 KiB

Open AccessArticle

Chitosan Hydrogel Beads Functionalized with Thymol-Loaded Solid Lipid–Polymer Hybrid Nanoparticles

by Taoran Wang and Yangchao Luo

Int. J. Mol. Sci. 2018, 19(10), 3112; https://doi.org/10.3390/ijms19103112 - 11 Oct 2018

Cited by 17 | Viewed by 7915

Abstract

In this study, the innovative and multifunctional nanoparticles–hydrogel nanocomposites made with chitosan hydrogel beads and solid lipid–polymer hybrid nanoparticles (SLPN) were prepared through conjugation between SLPN and chitosan beads. The SLPNs were first fabricated via coating the bovine serum albumin (BSA)-emulsified solid lipid [...] Read more.

In this study, the innovative and multifunctional nanoparticles–hydrogel nanocomposites made with chitosan hydrogel beads and solid lipid–polymer hybrid nanoparticles (SLPN) were prepared through conjugation between SLPN and chitosan beads. The SLPNs were first fabricated via coating the bovine serum albumin (BSA)-emulsified solid lipid nanoparticles with oxidized dextran. The aldehyde groups of the oxidized dextran on the surface of the SLPN enabled an in situ conjugation with the chitosan beads through the Schiff base linkage. The obtained nano-on-beads composite exhibited a spherical shape with a homogeneous size distribution. The successful conjugation of SLPN on the chitosan beads was confirmed by a Fourier transform infrared spectroscopy and a scanning electron microscope. The effects of the beads dosage (50, 100, 200, and 300 beads) and the incubation duration (30, 60, 90, 120, and 150 min) on the conjugation efficiency of SLPN onto the beads were comprehensively optimized. The optimal formulations were found to be a 200 bead dosage, with 30–90 min incubation duration groups. The optimal formulations were then used to encapsulate thymol, an antibacterial agent, which was studied as a model compound. After encapsulation, the thymol exhibited sustained release profiles in the phosphate buffer saline. The as-prepared nanoparticles–hydrogel nanocomposites reported in this proof-of-concept study hold promising features as a controlled-release antibacterial approach for improving food safety. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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13 pages, 2453 KiB

Open AccessArticle

Involvement of Endocytosis in the Transdermal Penetration Mechanism of Ketoprofen Nanoparticles

by Noriaki Nagai, Fumihiko Ogata, Miyu Ishii, Yuya Fukuoka, Hiroko Otake, Yosuke Nakazawa and Naohito Kawasaki

Int. J. Mol. Sci. 2018, 19(7), 2138; https://doi.org/10.3390/ijms19072138 - 23 Jul 2018

Cited by 32 | Viewed by 6364

Abstract

We previously designed a novel transdermal formulation containing ketoprofen solid nanoparticles (KET-NPs formulation), and showed that the skin penetration from the KET-NPs formulation was higher than that of a transdermal formulation containing ketoprofen microparticles (KET-MPs formulation). However, the precise mechanism for the skin [...] Read more.

We previously designed a novel transdermal formulation containing ketoprofen solid nanoparticles (KET-NPs formulation), and showed that the skin penetration from the KET-NPs formulation was higher than that of a transdermal formulation containing ketoprofen microparticles (KET-MPs formulation). However, the precise mechanism for the skin penetration from the KET-NPs formulation was not clear. In this study we investigated whether energy-dependent endocytosis relates to the transdermal delivery from a 1.5% KET-NPs formulation. Transdermal formulations were prepared by a bead mill method using additives including methylcellulose and carbopol 934. The mean particle size of the ketoprofen nanoparticles was 98.3 nm. Four inhibitors of endocytosis dissolved in 0.5% DMSO (54 μM nystatin, a caveolae-mediated endocytosis inhibitor; 40 μM dynasore, a clathrin-mediated endocytosis inhibitor; 2 μM rottlerin, a macropinocytosis inhibitor; 10 μM cytochalasin D, a phagocytosis inhibitor) were used in this study. In the transdermal penetration study using a Franz diffusion cell, skin penetration through rat skin treated with cytochalasin D was similar to the control (DMSO) group. In contrast to the results for cytochalasin D, skin penetration from the KET-NPs formulation was significantly decreased by treatment with nystatin, dynasore or rottlerin with penetrated ketoprofen concentration-time curves (AUC) values 65%, 69% and 73% of control, respectively. Furthermore, multi-treatment with all three inhibitors (nystatin, dynasore and rottlerin) strongly suppressed the skin penetration from the KET-NPs formulation with an AUC value 13.4% that of the control. In conclusion, we found that caveolae-mediated endocytosis, clathrin-mediated endocytosis and macropinocytosis are all related to the skin penetration from the KET-NPs formulation. These findings provide significant information for the design of nanomedicines in transdermal formulations. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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19 pages, 3063 KiB

Open AccessArticle

Silver Nanoparticles: Two-Faced Neuronal Differentiation-Inducing Material in Neuroblastoma (SH-SY5Y) Cells

by Ahmed Abdal Dayem, Soo Bin Lee, Hye Yeon Choi and Ssang-Goo Cho

Int. J. Mol. Sci. 2018, 19(5), 1470; https://doi.org/10.3390/ijms19051470 - 15 May 2018

Cited by 16 | Viewed by 5757

Abstract

We have previously demonstrated the potential of biologically synthesized silver nanoparticles (AgNP) in the induction of neuronal differentiation of human neuroblastoma, SH-SY5Y cells; we aimed herein to unveil its molecular mechanism in comparison to the well-known neuronal differentiation-inducing agent, all-trans-retinoic acid (RA). AgNP-treated [...] Read more.

We have previously demonstrated the potential of biologically synthesized silver nanoparticles (AgNP) in the induction of neuronal differentiation of human neuroblastoma, SH-SY5Y cells; we aimed herein to unveil its molecular mechanism in comparison to the well-known neuronal differentiation-inducing agent, all-trans-retinoic acid (RA). AgNP-treated SH-SY5Y cells showed significantly higher reactive oxygen species (ROS) generation, stronger mitochondrial membrane depolarization, lower dual-specificity phosphatase expression, higher extracellular-signal-regulated kinase (ERK) phosphorylation, lower AKT phosphorylation, and lower expression of the genes encoding the antioxidant enzymes than RA-treated cells. Notably, pretreatment with N-acetyl-l-cysteine significantly abolished AgNP-induced neuronal differentiation, but not in that induced by RA. ERK inhibition, but not AKT inhibition, suppresses neurite growth that is induced by AgNP. Taken together, our results uncover the pivotal contribution of ROS in the AgNP-induced neuronal differentiation mechanism, which is different from that of RA. However, the negative consequence of AgNP-induced neurite growth may be high ROS generation and the downregulation of the expression of the genes encoding the antioxidant enzymes, which prompts the future consideration and an in-depth study of the application of AgNP-differentiated cells in neurodegenerative disease therapy. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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18 pages, 4739 KiB

Open AccessArticle

Effect of Amelogenin Coating of a Nano-Modified Titanium Surface on Bioactivity

by Chisato Terada, Satoshi Komasa, Tetsuji Kusumoto, Takayoshi Kawazoe and Joji Okazaki

Int. J. Mol. Sci. 2018, 19(5), 1274; https://doi.org/10.3390/ijms19051274 - 24 Apr 2018

Cited by 17 | Viewed by 6332

Abstract

The interactions between implants and host tissues depend on several factors. In particular, a growing body of evidence has demonstrated that the surface texture of an implant influences the response of the surrounding cells. The purpose of this study is to develop new [...] Read more.

The interactions between implants and host tissues depend on several factors. In particular, a growing body of evidence has demonstrated that the surface texture of an implant influences the response of the surrounding cells. The purpose of this study is to develop new implant materials aiming at the regeneration of periodontal tissues as well as hard tissues by coating nano-modified titanium with amelogenin, which is one of the main proteins contained in Emdogain^®. We confirmed by quartz crystal microbalance evaluation that amelogenin is easy to adsorb onto the nano-modified titanium surface as a coating. Scanning electron microscopy, scanning probe microscopy, X-ray photoelectron spectroscopy, and Fourier-transform infrared spectroscopy analyses confirmed that amelogenin coated the nano-modified titanium surface following alkali-treatment. In vitro evaluation using rat bone marrow and periodontal ligament cells revealed that the initial adhesion of both cell types and the induction of hard tissue differentiation such as cementum were improved by amelogenin coating. Additionally, the formation of new bone in implanted surrounding tissues was observed in in vivo evaluation using rat femurs. Together, these results suggest that this material may serve as a new implant material with the potential to play a major role in the advancement of clinical dentistry. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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13 pages, 38053 KiB

Open AccessArticle

In Vitro and In Vivo Osteogenic Activity of Titanium Implants Coated by Pulsed Laser Deposition with a Thin Film of Fluoridated Hydroxyapatite

by Luyuan Chen, Satoshi Komasa, Yoshiya Hashimoto, Shigeki Hontsu and Joji Okazaki

Int. J. Mol. Sci. 2018, 19(4), 1127; https://doi.org/10.3390/ijms19041127 - 10 Apr 2018

Cited by 32 | Viewed by 4986

Abstract

To enhance biocompatibility, osteogenesis, and osseointegration, we coated titanium implants, by krypton fluoride (KrF) pulsed laser deposition, with a thin film of fluoridated hydroxyapatite (FHA). Coating was confirmed by scanning electron microscopy (SEM) and scanning probe microscopy (SPM), while physicochemical properties were evaluated [...] Read more.

To enhance biocompatibility, osteogenesis, and osseointegration, we coated titanium implants, by krypton fluoride (KrF) pulsed laser deposition, with a thin film of fluoridated hydroxyapatite (FHA). Coating was confirmed by scanning electron microscopy (SEM) and scanning probe microscopy (SPM), while physicochemical properties were evaluated by attenuated reflectance Fourier transform infrared spectroscopy (ATR-FTIR). Calcium deposition, osteocalcin production, and expression of osteoblast genes were significantly higher in rat bone marrow mesenchymal stem cells seeded on FHA-coated titanium than in cells seeded on uncoated titanium. Implantation into rat femurs also showed that the FHA-coated material had superior osteoinductive and osseointegration activity in comparison with that of traditional implants, as assessed by microcomputed tomography and histology. Thus, titanium coated with FHA holds promise as a dental implant material. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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13 pages, 8447 KiB

Open AccessArticle

HER2-Targeted Multifunctional Silica Nanoparticles Specifically Enhance the Radiosensitivity of HER2-Overexpressing Breast Cancer Cells

by Haruka Yamaguchi, Kazuhide Hayama, Ichiro Sasagawa, Yasuo Okada, Tomoyuki Kawase, Norio Tsubokawa and Makoto Tsuchimochi

Int. J. Mol. Sci. 2018, 19(3), 908; https://doi.org/10.3390/ijms19030908 - 19 Mar 2018

Cited by 25 | Viewed by 6125

Abstract

We investigated the effects of targeted functionalized silica nanoparticles on the radiosensitivity of cancer cells. Better control of the local concentration of silica nanoparticles may facilitate their use as an adjuvant in conjunction with ionizing radiation to target cancer cells while preventing damage [...] Read more.

We investigated the effects of targeted functionalized silica nanoparticles on the radiosensitivity of cancer cells. Better control of the local concentration of silica nanoparticles may facilitate their use as an adjuvant in conjunction with ionizing radiation to target cancer cells while preventing damage to normal cells. Hyperbranched polyamidoamine (PAMAM) was grafted onto the surface of amorphous silica nanoparticles to functionalize them. The PAMAM-coated silica nanoparticles (PCSNs) were then conjugated with fluorescent dyes. Anti-HER2 antibodies were covalently attached to the labeled PCSNs. The HER2-overexpressing SK-BR3 breast cancer cell line was incubated in medium containing the PCSN probes. After incubation; the cells were exposed to X-ray radiation. Cells were counted in all samples using cell proliferation assays; and apoptotic cells were detected. The cell survival results showed that the combination of the targeted PCSN probes and radiation reduced the survival rate of SK-BR3 cells to a greater extent than when either PCSN probes, PCSNs or radiation were applied individually. The results also showed an increase in apoptosis in the SK-BR3 cells that internalized the PCSN probes and were then irradiated. Based on these data, PCSN probes act as specific radiosensitizing agents for HER2-overexpressing cells. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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28 pages, 5856 KiB

Open AccessArticle

Combined Subchronic Toxicity of Aluminum (III), Titanium (IV) and Silicon (IV) Oxide Nanoparticles and Its Alleviation with a Complex of Bioprotectors

by Ilzira A. Minigalieva, Boris A. Katsnelson, Larisa I. Privalova, Marina P. Sutunkova, Vladimir B. Gurvich, Vladimir Y. Shur, Ekaterina V. Shishkina, Irene E. Valamina, Oleg H. Makeyev, Vladimir G. Panov, Anatoly N. Varaksin, Tatiana V. Bushueva, Renata R. Sakhautdinova, Svetlana V. Klinova, Svetlana N. Solovyeva and Ekaterina Y. Meshtcheryakova

Int. J. Mol. Sci. 2018, 19(3), 837; https://doi.org/10.3390/ijms19030837 - 13 Mar 2018

Cited by 28 | Viewed by 4658

Abstract

Stable suspensions of metal/metalloid oxide nanoparticles (MeO-NPs) obtained by laser ablation of 99.99% pure elemental aluminum, titanium or silicon under a layer of deionized water were used separately, or in three binary combinations, or in a ternary combination to induce subchronic intoxications in [...] Read more.

Stable suspensions of metal/metalloid oxide nanoparticles (MeO-NPs) obtained by laser ablation of 99.99% pure elemental aluminum, titanium or silicon under a layer of deionized water were used separately, or in three binary combinations, or in a ternary combination to induce subchronic intoxications in rats. To this end, the MeO-NPs were repeatedly injected intraperitoneally (i.p.) 18 times during 6 weeks before measuring a large number of functional, biochemical, morphological and cytological indices for the organism’s status. In many respects, the Al₂O₃-NP was found to be the most toxic species alone and the most dangerous component of the combinations studied. Mathematical modeling with the help of the Response Surface Methodology showed that, as well as in the case of any other binary toxic combinations previously investigated by us, the organism’s response to a simultaneous exposure to any two of the MeO-NP species under study was characterized by a complex interaction between all possible types of combined toxicity (additivity, subadditivity or superadditivity of unidirectional action and different variants of opposite effects) depending on which outcome this type was estimated for and on effect and dose levels. With any third MeO-NP species acting in the background, the type of combined toxicity displayed by the other two remained virtually the same or changed significantly, becoming either more or less unfavorable. Various harmful effects produced by the (Al₂O₃-NP + TiO₂-NP + SiO₂-NP)-combination, including its genotoxicity, were substantially attenuated by giving the rats per os during the entire exposure period a complex of innocuous bioactive substances expected to increase the organism’s antitoxic resistance. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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11 pages, 3133 KiB

Open AccessArticle

“Nano-Ginseng” for Enhanced Cytotoxicity AGAINST Cancer Cells

by Lin Dai, Weiyan Zhu, Chuanling Si and Jiandu Lei

Int. J. Mol. Sci. 2018, 19(2), 627; https://doi.org/10.3390/ijms19020627 - 23 Feb 2018

Cited by 22 | Viewed by 5466

Abstract

Panax ginseng has high medicinal and health values. However, the various and complex components of ginseng may interact with each other, thus reducing and even reversing therapeutic effects. In this study, we designed and fabricated a novel “nano-ginseng” with definite ingredients, ginsenoside Rb1/protopanaxadiol [...] Read more.

Panax ginseng has high medicinal and health values. However, the various and complex components of ginseng may interact with each other, thus reducing and even reversing therapeutic effects. In this study, we designed and fabricated a novel “nano-ginseng” with definite ingredients, ginsenoside Rb1/protopanaxadiol nanoparticles (Rb1/PPD NPs), completely based on the protopanaxadiol-type extracts. The optimized nano-formulations demonstrated an appropriate size (~110 nm), high drug loading efficiency (~96.8%) and capacity (~27.9 wt %), long half-time in systemic circulation (nine-fold longer than free PPD), better antitumor effects in vitro and in vivo, higher accumulation at the tumor site and reduced damage to normal tissues. Importantly, this process of “nano-ginseng” production is a simple, scalable, green economy process. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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16 pages, 4467 KiB

Open AccessArticle

Effects of Interactions between ZnO Nanoparticles and Saccharides on Biological Responses

by Mi-Ran Go, Jin Yu, Song-Hwa Bae, Hyeon-Jin Kim and Soo-Jin Choi

Int. J. Mol. Sci. 2018, 19(2), 486; https://doi.org/10.3390/ijms19020486 - 6 Feb 2018

Cited by 35 | Viewed by 4958

Abstract

Zinc oxide (ZnO) nanoparticles (NPs) are widely used as a Zn supplement, because Zn plays a role in many cellular and immune functions but public concern about their potentially undesirable effects on the human body is growing. When NPs are added in food [...] Read more.

Zinc oxide (ZnO) nanoparticles (NPs) are widely used as a Zn supplement, because Zn plays a role in many cellular and immune functions but public concern about their potentially undesirable effects on the human body is growing. When NPs are added in food matrices, interactions between NPs and food components occur, which can affect biological systems. In this study, interactions between ZnO NPs and saccharides were investigated by measuring changes in hydrodynamic radius, zeta potential and solubility and by quantifying amounts of adsorbed saccharides on NPs; acacia honey, sugar mixtures (containing equivalent amounts of fructose, glucose, sucrose and maltose) and monosaccharide solutions were used as model compounds. Biological responses of NPs dispersed in different saccharides were also evaluated in human intestinal cells and rats in terms of cytotoxicity, cellular uptake, intestinal transport and oral absorption. The results demonstrate that the hydrodynamic radii and zeta potentials of NPs were highly affected by saccharides. In addition, trace nutrients influenced NP/saccharide interactions and interactive effects between saccharides on the interactions were found. NPs in all saccharides increased inhibition of cell proliferation and enhanced cellular uptake. Oral absorption of NPs was highly enhanced by 5% glucose, which is in-line with intestinal transport result. These findings show that ZnO NPs interact with saccharides and these interactions affects biological responses. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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19 pages, 7060 KiB

Open AccessArticle

Amorphous, Smart, and Bioinspired Polyphosphate Nano/Microparticles: A Biomaterial for Regeneration and Repair of Osteo-Articular Impairments In-Situ

by Werner E. G. Müller, Meik Neufurth, Shunfeng Wang, Maximilian Ackermann, Rafael Muñoz-Espí, Qingling Feng, Qiang Lu, Heinz C. Schröder and Xiaohong Wang

Int. J. Mol. Sci. 2018, 19(2), 427; https://doi.org/10.3390/ijms19020427 - 31 Jan 2018

Cited by 23 | Viewed by 6385

Abstract

Using femur explants from mice as an in vitro model, we investigated the effect of the physiological polymer, inorganic polyphosphate (polyP), on differentiation of the cells of the bone marrow in their natural microenvironment into the osteogenic and chondrogenic lineages. In the form [...] Read more.

Using femur explants from mice as an in vitro model, we investigated the effect of the physiological polymer, inorganic polyphosphate (polyP), on differentiation of the cells of the bone marrow in their natural microenvironment into the osteogenic and chondrogenic lineages. In the form of amorphous Ca-polyP nano/microparticles, polyP retains its function to act as both an intra- and extracellular metabolic fuel and a stimulus eliciting morphogenetic signals. The method for synthesis of the nano/microparticles with the polyanionic polyP also allowed the fabrication of hybrid particles with the bisphosphonate zoledronic acid, a drug used in therapy of bone metastases in cancer patients. The results revealed that the amorphous Ca-polyP particles promote the growth/viability of mesenchymal stem cells, as well as the osteogenic and chondrogenic differentiation of the bone marrow cells in rat femur explants, as revealed by an upregulation of the expression of the transcription factors SOX9 (differentiation towards osteoblasts) and RUNX2 (chondrocyte differentiation). In parallel to this bone anabolic effect, incubation of the femur explants with these particles significantly reduced the expression of the gene encoding the osteoclast bone-catabolic enzyme, cathepsin-K, while the expression of the tartrate-resistant acid phosphatase remained unaffected. The gene expression data were supported by the finding of an increased mineralization of the cells in the femur explants in response to the Ca-polyP particles. Finally, we show that the hybrid particles of polyP complexed with zoledronic acid exhibit both the cytotoxic effect of the bisphosphonate and the morphogenetic and mineralization inducing activity of polyP. Our results suggest that the Ca-polyP nano/microparticles are not only a promising scaffold material for repairing long bone osteo-articular damages but can also be applied, as a hybrid with zoledronic acid, as a drug delivery system for treatment of bone metastases. The polyP particles are highlighted as genuine, smart, bioinspired nano/micro biomaterials. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Open AccessArticle

Bioaccumulation and Toxicity of Carbon Nanoparticles Suspension Injection in Intravenously Exposed Mice

by Ping Xie, Sheng-Tao Yang, Tiantian He, Shengnan Yang and Xiao-Hai Tang

Int. J. Mol. Sci. 2017, 18(12), 2562; https://doi.org/10.3390/ijms18122562 - 29 Nov 2017

Cited by 44 | Viewed by 5475

Abstract

Carbon nanoparticles suspension injection (CNSI) has been widely used in tumor drainage lymph node mapping, and its new applications in drug delivery, photothermal therapy, and so on have been extensively investigated. To develop new clinical applications, the toxicity of CNSI after intravenous exposure [...] Read more.

Carbon nanoparticles suspension injection (CNSI) has been widely used in tumor drainage lymph node mapping, and its new applications in drug delivery, photothermal therapy, and so on have been extensively investigated. To develop new clinical applications, the toxicity of CNSI after intravenous exposure should be thoroughly investigated to ensure its safe use. Herein, we studied the bioaccumulation of CNSI in reticuloendothelial system (RES) organs and the corresponding toxicity to mice. After the intravenous injection of CNSI, no abnormal behavior of mice was observed during the 28-day observation period. The body weight increases were similar among the exposed groups and the control group. The parameters of hematology and serum biochemistry remained nearly unchanged, with very few of them showing significant changes. The low toxicity of CNSI was also reflected by the unchanged histopathological characteristics of these organs. The injection of CNSI did not induce higher apoptosis levels either. The slight oxidative stress was observed in RES organs at high dosages at day 7 post-exposure. The implication to the clinical applications and toxicological evaluations of carbon nanomaterials is discussed. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Open AccessArticle

Cytotoxicity of Poly(Alkyl Cyanoacrylate) Nanoparticles

by Einar Sulheim, Tore-Geir Iversen, Vu To Nakstad, Geir Klinkenberg, Håvard Sletta, Ruth Schmid, Anne Rein Hatletveit, Ane Marit Wågbø, Anders Sundan, Tore Skotland, Kirsten Sandvig and Ýrr Mørch

Int. J. Mol. Sci. 2017, 18(11), 2454; https://doi.org/10.3390/ijms18112454 - 18 Nov 2017

Cited by 44 | Viewed by 6400

Abstract

Although nanotoxicology has become a large research field, assessment of cytotoxicity is often reduced to analysis of one cell line only. Cytotoxicity of nanoparticles is complex and should, preferentially, be evaluated in several cell lines with different methods and on multiple nanoparticle batches. [...] Read more.

Although nanotoxicology has become a large research field, assessment of cytotoxicity is often reduced to analysis of one cell line only. Cytotoxicity of nanoparticles is complex and should, preferentially, be evaluated in several cell lines with different methods and on multiple nanoparticle batches. Here we report the toxicity of poly(alkyl cyanoacrylate) nanoparticles in 12 different cell lines after synthesizing and analyzing 19 different nanoparticle batches and report that large variations were obtained when using different cell lines or various toxicity assays. Surprisingly, we found that nanoparticles with intermediate degradation rates were less toxic than particles that were degraded faster or more slowly in a cell-free system. The toxicity did not vary significantly with either the three different combinations of polyethylene glycol surfactants or with particle size (range 100–200 nm). No acute pro- or anti-inflammatory activity on cells in whole blood was observed. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Open AccessArticle

Targeted Delivery of siRNA with pH-Responsive Hybrid Gold Nanostars for Cancer Treatment

by Hongyan Zhu, Wanwan Liu, Ziting Cheng, Ke Yao, Yu Yang, Bohui Xu and Gaoxing Su

Int. J. Mol. Sci. 2017, 18(10), 2029; https://doi.org/10.3390/ijms18102029 - 22 Sep 2017

Cited by 30 | Viewed by 5604

Abstract

In this work, we report the engineering of gold nanostars (GNS) to deliver small interfering RNA (siRNA) into HepG2 cells. The ligand DG-PEG-Lipoic acid (LA)-Lys-9R (hydrazone) was designed to functionalize GNS, and create the nanoparticles named as 9R/DG-GNS (hydrazone). In the ligand, 2-deoxyglucose [...] Read more.

In this work, we report the engineering of gold nanostars (GNS) to deliver small interfering RNA (siRNA) into HepG2 cells. The ligand DG-PEG-Lipoic acid (LA)-Lys-9R (hydrazone) was designed to functionalize GNS, and create the nanoparticles named as 9R/DG-GNS (hydrazone). In the ligand, 2-deoxyglucose (DG) is the targeting molecule, polyethylene glycol (PEG) helps to improve the dispersity and biocompatibility, 9-poly-d-arginine (9R) is employed to provide a positive surface charge and adsorb negative siRNA, and hydrazone bonds are pH-responsive and can avoid receptor-mediated endosomal recycling. Compared to GNS alone, 9R/DG-GNS (hydrazone) showed superior transfection efficiency. The expressions of cyclooxygenase-2 (COX-2) in HepG2 and SGC7901 cells were significantly suppressed by siRNA/9R/DG-GNS (hydrazone) complex. Notably, 9R/DG-GNS (hydrazone) possessed low cytotoxicity even at high concentrations in both normal cells and tumor cells. The combination treatment of siRNA/9R/DG-GNS (hydrazone) complex inhibited the cell growth rate by more than 75%. These results verified that the pH-responsive GNS complex is a promising siRNA delivery system for cancer therapy, and it is anticipated that near-infrared absorbing GNS with good photothermal conversion efficiency can be potentially used for photothermal therapy of tumors. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Open AccessCommunication

Therapeutic Efficacy of the Novel Stimuli-Sensitive Nano-Ferritins Containing Doxorubicin in a Head and Neck Cancer Model

by Verena Damiani, Elisabetta Falvo, Giulio Fracasso, Luca Federici, Martina Pitea, Vincenzo De Laurenzi, Gianluca Sala and Pierpaolo Ceci

Int. J. Mol. Sci. 2017, 18(7), 1555; https://doi.org/10.3390/ijms18071555 - 18 Jul 2017

Cited by 34 | Viewed by 6012

Abstract

Doxorubicin is employed alone or in combination for the treatment of several hematological and solid malignancies; despite its efficacy, there are associated cardiotoxicity limits both in its application in patients with heart disease risk factors and also in its long-term use. HFt-MP-PAS40 is [...] Read more.

Doxorubicin is employed alone or in combination for the treatment of several hematological and solid malignancies; despite its efficacy, there are associated cardiotoxicity limits both in its application in patients with heart disease risk factors and also in its long-term use. HFt-MP-PAS40 is a genetically engineered human ferritin heavy chain (HFt)-based construct able to efficiently entrap and deliver doxorubicin to cancer cells. HF-MP-PAS contains a short motif sequence (defined as MP) responsive to proteolytic cleavage by tumor matrix metalloproteases (MMPs), located between each HFt subunit and a masking polypeptide sequence rich in proline (P), alanine (A), and serine (S) residues (PAS). This carrier displayed excellent therapeutic efficacy in a xenogenic pancreatic cancer model in vivo, leading to a significant increase in overall animal survival in treated mice. Herein, we describe the HFt-MP-PAS40-Dox efficacy against squamous cell carcinomas of the head and neck (HNSCC) with the goal of validating the application of our nano-drug for the treatment of different solid tumors. In addition, a tolerability study in healthy mice was also performed. The results indicate that HFt-MP-PAS40-Dox produced increased anti-tumor effects both in vitro and in vivo in comparison to the free drug in several HNSCC cell lines. In the acute toxicity studies, the maximum tolerated dose (MTD) of HFt-MP-PAS40-Dox was about 3.5 higher than the free drug: 25 mg/kg versus 7 mg/kg doxorubicin equivalents. Importantly, evaluation of heart tissues provided evidence that doxorubicin is less cardio-toxic when encapsulated inside the ferritin carrier. In conclusion, HFt-MP-PAS40-Dox may be administered safely at higher doses compared with the free drug, resulting in superior efficacy to control HNSCC malignancies. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Open AccessArticle

Effects of Titanium Mesh Surfaces-Coated with Hydroxyapatite/β-Tricalcium Phosphate Nanotubes on Acetabular Bone Defects in Rabbits

by Thuy-Duong Thi Nguyen, Tae-Sung Bae, Dae-hyeok Yang, Myung-sik Park and Sun-jung Yoon

Int. J. Mol. Sci. 2017, 18(7), 1462; https://doi.org/10.3390/ijms18071462 - 7 Jul 2017

Cited by 1 | Viewed by 6016

Abstract

The management of severe acetabular bone defects in revision reconstructive orthopedic surgery is challenging. In this study, cyclic precalcification (CP) treatment was used on both nanotube-surface Ti-mesh and a bone graft substitute for the acetabular defect model, and its effects were assessed in [...] Read more.

The management of severe acetabular bone defects in revision reconstructive orthopedic surgery is challenging. In this study, cyclic precalcification (CP) treatment was used on both nanotube-surface Ti-mesh and a bone graft substitute for the acetabular defect model, and its effects were assessed in vitro and in vivo. Nanotube-Ti mesh coated with hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) was manufactured by an anodizing and a sintering method, respectively. An 8 mm diameter defect was created on each acetabulum of eight rabbits, then treated by grafting materials and covered by Ti meshes. At four and eight weeks, postoperatively, biopsies were performed for histomorphometric analyses. The newly-formed bone layers under cyclic precalcified anodized Ti (CP-AT) meshes were superior with regard to the mineralized area at both four and eight weeks, as compared with that under untreated Ti meshes. Active bone regeneration at 2–4 weeks was stronger than at 6–8 weeks, particularly with treated biphasic ceramic (p < 0.05). CP improved the bioactivity of Ti meshes and biphasic grafting materials. Moreover, the precalcified nanotubular Ti meshes could enhance early contact bone formation on the mesh and, therefore, may reduce the collapse of Ti meshes into the defect, increasing the sufficiency of acetabular reconstruction. Finally, cyclic precalcification did not affect bone regeneration by biphasic grafting materials in vivo. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Open AccessArticle

Prevention of Oxidized Low Density Lipoprotein-Induced Endothelial Cell Injury by DA-PLGA-PEG-cRGD Nanoparticles Combined with Ultrasound

by Zhaojun Li, Hui Huang, Lili Huang, Lianfang Du, Ying Sun and Yourong Duan

Int. J. Mol. Sci. 2017, 18(4), 815; https://doi.org/10.3390/ijms18040815 - 13 Apr 2017

Cited by 14 | Viewed by 5463

Abstract

In general, atherosclerosis is considered to be a form of chronic inflammation. Dexamethasone has anti-inflammatory effects in atherosclerosis, but it was not considered for long-term administration on account of a poor pharmacokinetic profile and adverse side effects. Nanoparticles in which drugs can be [...] Read more.

In general, atherosclerosis is considered to be a form of chronic inflammation. Dexamethasone has anti-inflammatory effects in atherosclerosis, but it was not considered for long-term administration on account of a poor pharmacokinetic profile and adverse side effects. Nanoparticles in which drugs can be dissolved, encapsulated, entrapped or chemically attached to the particle surface have abilities to incorporate dexamethasone and to be used as controlled or targeted drug delivery system. Long circulatory polymeric nanoparticles present as an assisting approach for controlled and targeted release of the encapsulated drug at the atherosclerotic site. Polymeric nanoparticles combined with ultrasound (US) are widely applied in cancer treatment due to their time applications, low cost, simplicity, and safety. However, there are few studies on atherosclerosis treatment using polymeric nanoparticles combined with US. In this study, targeted dexamethasone acetate (DA)-loaded poly (lactide-glycolide)-polyethylene glycol-cRGD (PLGA-PEG-cRGD) nanoparticles (DA-PLGA-PEG-cRGD NPs) were prepared by the emulsion-evaporation method using cRGD modified PLGA-PEG polymeric materials (PLGA-PEG-cRGD) prepared as the carrier. The average particle size of DA-PLGA-PEG-cRGD NPs was 221.6 ± 0.9 nm. Morphology of the nanoparticles was spherical and uniformly dispersed. In addition, the DA released profiles suggested that ultrasound could promote drug release from the nanocarriers and accelerate the rate of release. In vitro, the cellular uptake process of fluorescein isothiocyanate (FITC)@DA-PLGA-PEG-cRGD NPs combined with US into the damaged human umbilical vein endothelial cells (HUVECs) indicated that US promoted rapid intracellular uptake of FITC@DA- PLGA-PEG-cRGD NPs. The cell viability of DA-PLGA-PEG-cRGD NPs combined with US reached 91.9% ± 0.2%, which demonstrated that DA-PLGA-PEG-cRGD NPs combined with US had a positive therapeutic effect on damaged HUVECs. Overall, DA-PLGA-PEG-cRGD NPs in combination with US may provide a promising drug delivery system to enhance the therapeutic effects of these chemotherapeutics at the cellular level. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Open AccessArticle

Bioactivity of NANOZR Induced by Alkali Treatment

by Mariko Nishizaki, Satoshi Komasa, Yoichiro Taguchi, Hiroshi Nishizaki and Joji Okazaki

Int. J. Mol. Sci. 2017, 18(4), 780; https://doi.org/10.3390/ijms18040780 - 6 Apr 2017

Cited by 15 | Viewed by 4723 | Correction

Abstract

In recent years, zirconia has been a recognized implant material in clinical dentistry. In the present study, we investigated the performance of an alkali-modified ceria-stabilized tetragonal ZrO₂ polycrystalline ceramic-based nanostructured zirconia/alumina composite (NANOZR) implant by assessing surface morphology and composition, wettability, bovine [...] Read more.

In recent years, zirconia has been a recognized implant material in clinical dentistry. In the present study, we investigated the performance of an alkali-modified ceria-stabilized tetragonal ZrO₂ polycrystalline ceramic-based nanostructured zirconia/alumina composite (NANOZR) implant by assessing surface morphology and composition, wettability, bovine serum albumin adsorption rate, rat bone marrow (RBM) cell attachment, and capacity for inducing bone differentiation. NANOZR surfaces without and with alkali treatment served as the control and test groups, respectively. RBM cells were seeded in a microplate with the implant and cultured in osteogenic differentiation medium, and their differentiation was evaluated by measuring alkaline phosphatase (ALP) activity, osteocalcin (OCN) production, calcium deposition, and osteogenic gene expression. The alkali-treated NANOZR surface increased ALP activity, OCN production, calcium deposition, and osteogenesis-related gene expression in attached RBM cells. These data suggest that alkali treatment enhances the osteogenesis-inducing capacity of NANOZR implants and may therefore improve their biointegration into alveolar bone. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Effects of Silver Nanoparticles on Multiple Drug-Resistant Strains of Staphylococcus aureus and Pseudomonas aeruginosa from Mastitis-Infected Goats: An Alternative Approach for Antimicrobial Therapy

by Yu-Guo Yuan, Qiu-Ling Peng and Sangiliyandi Gurunathan

Int. J. Mol. Sci. 2017, 18(3), 569; https://doi.org/10.3390/ijms18030569 - 6 Mar 2017

Cited by 259 | Viewed by 12559

Abstract

Recently, silver nanoparticles (AgNPs) have been widely used in various applications as antimicrobial agents, anticancer, diagnostics, biomarkers, cell labels, and drug delivery systems for the treatment of various diseases. Microorganisms generally acquire resistance to antibiotics through the course of antibacterial therapy. Multi-drug resistance [...] Read more.

Recently, silver nanoparticles (AgNPs) have been widely used in various applications as antimicrobial agents, anticancer, diagnostics, biomarkers, cell labels, and drug delivery systems for the treatment of various diseases. Microorganisms generally acquire resistance to antibiotics through the course of antibacterial therapy. Multi-drug resistance (MDR) has become a growing problem in the treatment of infectious diseases, and the widespread use of broad-spectrum antibiotics has resulted in the development of antibiotic resistance by numerous human and animal bacterial pathogens. As a result, an increasing number of microorganisms are resistant to multiple antibiotics causing continuing economic losses in dairy farming. Therefore, there is an urgent need for the development of alternative, cost-effective, and efficient antimicrobial agents that overcome antimicrobial resistance. Here, AgNPs synthesized using the bio-molecule quercetin were characterized using various analytical techniques. The synthesized AgNPs were highly spherical in shape and had an average size of 11 nm. We evaluated the efficacy of synthesized AgNPs against two MDR pathogenic bacteria, namely, Pseudomonas aeruginosa and Staphylococcus aureus, which were isolated from milk samples produced by mastitis-infected goats. The minimum inhibitory concentrations (MICs) of AgNPs against P. aeruginosa and S. aureus were found to be 1 and 2 μg/mL, respectively. Our findings suggest that AgNPs exert antibacterial effects in a dose- and time-dependent manner. Results from the present study demonstrate that the antibacterial activity of AgNPs is due to the generation of reactive oxygen species (ROS), malondialdehyde (MDA), and leakage of proteins and sugars in bacterial cells. Results of the present study showed that AgNP-treated bacteria had significantly lower lactate dehydrogenase activity (LDH) and lower adenosine triphosphate (ATP) levels compared to the control. Furthermore, AgNP-treated bacteria showed downregulated expression of glutathione (GSH), upregulation of glutathione S-transferase (GST), and downregulation of both superoxide dismutase (SOD) and catalase (CAT). These physiological and biochemical measurements were consistently observed in AgNP-treated bacteria, thereby suggesting that AgNPs can induce bacterial cell death. Thus, the above results represent conclusive findings on the mechanism of action of AgNPs against different types of bacteria. This study also demonstrates the promising use of nanoparticles as antibacterial agents for use in the biotechnology and biomedical industry. Furthermore, this study is the first to propose the mode of action of AgNPs against MDR pathogens isolated from goats infected with subclinical mastitis. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Open AccessArticle

Photoluminescent Gold Nanoclusters in Cancer Cells: Cellular Uptake, Toxicity, and Generation of Reactive Oxygen Species

by Marija Matulionyte, Dominyka Dapkute, Laima Budenaite, Greta Jarockyte and Ricardas Rotomskis

Int. J. Mol. Sci. 2017, 18(2), 378; https://doi.org/10.3390/ijms18020378 - 10 Feb 2017

Cited by 33 | Viewed by 7107

Abstract

In recent years, photoluminescent gold nanoclusters have attracted considerable interest in both fundamental biomedical research and practical applications. Due to their ultrasmall size, unique molecule-like optical properties, and facile synthesis gold nanoclusters have been considered very promising photoluminescent agents for biosensing, bioimaging, and [...] Read more.

In recent years, photoluminescent gold nanoclusters have attracted considerable interest in both fundamental biomedical research and practical applications. Due to their ultrasmall size, unique molecule-like optical properties, and facile synthesis gold nanoclusters have been considered very promising photoluminescent agents for biosensing, bioimaging, and targeted therapy. Yet, interaction of such ultra-small nanoclusters with cells and other biological objects remains poorly understood. Therefore, the assessment of the biocompatibility and potential toxicity of gold nanoclusters is of major importance before their clinical application. In this study, the cellular uptake, cytotoxicity, and intracellular generation of reactive oxygen species (ROS) of bovine serum albumin-encapsulated (BSA-Au NCs) and 2-(N-morpholino) ethanesulfonic acid (MES)capped photoluminescent gold nanoclusters (Au-MES NCs) were investigated. The results showed that BSA-Au NCs accumulate in cells in a similar manner as BSA alone, indicating an endocytotic uptake mechanism while ultrasmall Au-MES NCs were distributed homogeneously throughout the whole cell volume including cell nucleus. The cytotoxicity of BSA-Au NCs was negligible, demonstrating good biocompatibility of such BSA-protected Au NCs. In contrast, possibly due to ultrasmall size and thin coating layer, Au-MES NCs exhibited exposure time-dependent high cytotoxicity and higher reactivity which led to highly increased generation of reactive oxygen species. The results demonstrate the importance of the coating layer to biocompatibility and toxicity of ultrasmall photoluminescent gold nanoclusters. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Multifunctional Composite Microcapsules for Oral Delivery of Insulin

by Shaoping Sun, Na Liang, Xianfeng Gong, Weiwei An, Yoshiaki Kawashima, Fude Cui and Pengfei Yan

Int. J. Mol. Sci. 2017, 18(1), 54; https://doi.org/10.3390/ijms18010054 - 28 Dec 2016

Cited by 21 | Viewed by 6509

Abstract

In this study, we designed and developed a new drug delivery system of multifunctional composite microcapsules for oral administration of insulin. Firstly, in order to enhance the encapsulation efficiency, insulin was complexed with functional sodium deoxycholate to form insulin-sodium deoxycholate complex using hydrophobic [...] Read more.

In this study, we designed and developed a new drug delivery system of multifunctional composite microcapsules for oral administration of insulin. Firstly, in order to enhance the encapsulation efficiency, insulin was complexed with functional sodium deoxycholate to form insulin-sodium deoxycholate complex using hydrophobic ion pairing method. Then the complex was encapsulated into poly(lactide-co-glycolide) (PLGA) nanoparticles by emulsion solvent diffusion method. The PLGA nanoparticles have a mean size of 168 nm and a zeta potential of −29.2 mV. The encapsulation efficiency was increased to 94.2% for the complex. In order to deliver insulin to specific gastrointestinal regions and reduce the burst release of insulin from PLGA nanoparticles, hence enhancing the bioavailability of insulin, enteric targeting multifunctional composite microcapsules were further prepared by encapsulating PLGA nanoparticles into pH-sensitive hydroxypropyl methyl cellulose phthalate (HP55) using organic spray-drying method. A pH-dependent insulin release profile was observed for this drug delivery system in vitro. All these strategies help to enhance the encapsulation efficiency, control the drug release, and protect insulin from degradation. In diabetic fasted rats, administration of the composite microcapsules produced a great enhancement in the relative bioavailability, which illustrated that this formulation was an effective candidate for oral insulin delivery. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells

by Yun-Jung Choi, Jung-Hyun Park, Jae Woong Han, Eunsu Kim, Oh Jae-Wook, Seung Yoon Lee, Jin-Hoi Kim and Sangiliyandi Gurunathan

Int. J. Mol. Sci. 2016, 17(12), 2077; https://doi.org/10.3390/ijms17122077 - 12 Dec 2016

Cited by 36 | Viewed by 6201

Abstract

The cancer stem cell (CSC) hypothesis postulates that cancer cells are composed of hierarchically-organized subpopulations of cells with distinct phenotypes and tumorigenic capacities. As a result, CSCs have been suggested as a source of disease recurrence. Recently, silver nanoparticles (AgNPs) have been used [...] Read more.

The cancer stem cell (CSC) hypothesis postulates that cancer cells are composed of hierarchically-organized subpopulations of cells with distinct phenotypes and tumorigenic capacities. As a result, CSCs have been suggested as a source of disease recurrence. Recently, silver nanoparticles (AgNPs) have been used as antimicrobial, disinfectant, and antitumor agents. However, there is no study reporting the effects of AgNPs on ovarian cancer stem cells (OvCSCs). In this study, we investigated the cytotoxic effects of AgNPs and their mechanism of causing cell death in A2780 (human ovarian cancer cells) and OvCSCs derived from A2780. In order to examine these effects, OvCSCs were isolated and characterized using positive CSC markers including aldehyde dehydrogenase (ALDH) and CD133 by fluorescence-activated cell sorting (FACS). The anticancer properties of the AgNPs were evaluated by assessing cell viability, leakage of lactate dehydrogenase (LDH), reactive oxygen species (ROS), and mitochondrial membrane potential (mt-MP). The inhibitory effect of AgNPs on the growth of ovarian cancer cells and OvCSCs was evaluated using a clonogenic assay. Following 1–2 weeks of incubation with the AgNPs, the numbers of A2780 (bulk cells) and ALDH⁺/CD133⁺ colonies were significantly reduced. The expression of apoptotic and anti-apoptotic genes was measured by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Our observations showed that treatment with AgNPs resulted in severe cytotoxicity in both ovarian cancer cells and OvCSCs. In particular, AgNPs showed significant cytotoxic potential in ALDH⁺/CD133⁺ subpopulations of cells compared with other subpopulation of cells and also human ovarian cancer cells (bulk cells). These findings suggest that AgNPs can be utilized in the development of novel nanotherapeutic molecules for the treatment of ovarian cancers by specific targeting of the ALDH⁺/CD133⁺ subpopulation of cells. Full article

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Synthesis of Non-Toxic Silica Particles Stabilized by Molecular Complex Oleic-Acid/Sodium Oleate

by Catalin Ilie Spataru, Raluca Ianchis, Cristian Petcu, Cristina Lavinia Nistor, Violeta Purcar, Bogdan Trica, Sabina Georgiana Nitu, Raluca Somoghi, Elvira Alexandrescu, Florin Oancea and Dan Donescu

Int. J. Mol. Sci. 2016, 17(11), 1936; https://doi.org/10.3390/ijms17111936 - 19 Nov 2016

Cited by 10 | Viewed by 7274

Abstract

The present work is focused on the preparation of biocompatible silica particles from sodium silicate, stabilized by a vesicular system containing oleic acid (OLA) and its alkaline salt (OLANa). Silica nanoparticles were generated by the partial neutralization of oleic acid (OLA), with the [...] Read more.

The present work is focused on the preparation of biocompatible silica particles from sodium silicate, stabilized by a vesicular system containing oleic acid (OLA) and its alkaline salt (OLANa). Silica nanoparticles were generated by the partial neutralization of oleic acid (OLA), with the sodium cation present in the aqueous solutions of sodium silicate. At the molar ratio OLA/Na⁺ = 2:1, the molar ratio (OLA/OLANa = 1:1) required to form vesicles, in which the carboxyl and carboxylate groups have equal concentrations, was achieved. In order to obtain hydrophobically modified silica particles, octadecyltriethoxysilane (ODTES) was added in a sodium silicate sol–gel mixture at different molar ratios. The interactions between the octadecyl groups from the modified silica and the oleyl chains from the OLA/OLANa stabilizing system were investigated via simultaneous thermogravimetry (TG) and differential scanning calorimetry (DSC) (TG-DSC) analyses.A significant decrease in vaporization enthalpy and an increase in amount of ODTES were observed. Additionally, that the hydrophobic interaction between OLA and ODTES has a strong impact on the hybrids’ final morphology and on their textural characteristics was revealed. The highest hydrodynamic average diameter and the most negative ζ potential were recorded for the hybrid in which the ODTES/sodium silicate molar ratio was 1:5. The obtained mesoporous silica particles, stabilized by the OLA/OLANa vesicular system, may find application as carriers for hydrophobic bioactive molecules. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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A Novel Prostate-Specific Membrane-Antigen (PSMA) Targeted Micelle-Encapsulating Wogonin Inhibits Prostate Cancer Cell Proliferation via Inducing Intrinsic Apoptotic Pathway

by Hailong Zhang, Xiaogang Liu, Fengbo Wu, Feifei Qin, Ping Feng, Ting Xu, Xiang Li and Li Yang

Int. J. Mol. Sci. 2016, 17(5), 676; https://doi.org/10.3390/ijms17050676 - 17 May 2016

Cited by 26 | Viewed by 8964

Abstract

Prostate cancer (PCa) is a malignant tumor for which there are no effective treatment strategies. In this study, we developed a targeted strategy for prostate-specific membrane-antigen (PSMA)-positive PCa in vitro based on 2-(3-((S)-5-amino-1-carboxypentyl)ureido) pentanedioic acid (ACUPA) modified polyethylene glycol (PEG)-Cholesterol micelles [...] Read more.

Prostate cancer (PCa) is a malignant tumor for which there are no effective treatment strategies. In this study, we developed a targeted strategy for prostate-specific membrane-antigen (PSMA)-positive PCa in vitro based on 2-(3-((S)-5-amino-1-carboxypentyl)ureido) pentanedioic acid (ACUPA) modified polyethylene glycol (PEG)-Cholesterol micelles containing wogonin (WOG), which was named ACUPA-M-WOG. ACUPA-M-WOG was conventionally prepared using a self-assembling method, which produced stable particle size and ζ potential. Moreover, ACUPA-M-WOG showed good drug encapsulating capacity and drug release profiles. Fluorescence activated cell sorting (FACS) results suggested that ACUPA modified PEG-Cholesterol micelles could effectively enhance the drug uptake on PSMA(+) PCa cells, and the cytotoxicity of ACUPA-M-WOG was stronger than other controls according to in vitro cellular proliferation and apoptosis assays, separately through methyl thiazolyl tetrazolium (MTT) and Annexin V/Propidium Iodide (PI) staining. Finally, the molecular mechanisms of ACUPA-M-WOG’s effects on human PSMA(+) PCa were investigated, and were mainly the intrinsic or extrinsic apoptosis signaling pathways. The Western blot results suggested that ACUPA-M-WOG could enhance the WOG-induced apoptosis, which was mainly via the intrinsic signaling pathway rather than the extrinsic signaling pathway. In conclusion, ACUPA-M-WOG was successfully developed for WOG-selective delivery to PSMA(+) PCa cells and had stronger inhibition than free drugs, which might make it an effective strategy for PSMA(+) PCa. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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The Isolation of DNA by Polycharged Magnetic Particles: An Analysis of the Interaction by Zeta Potential and Particle Size

by Yazan Haddad, Kledi Xhaxhiu, Pavel Kopel, David Hynek, Ondrej Zitka and Vojtech Adam

Int. J. Mol. Sci. 2016, 17(4), 550; https://doi.org/10.3390/ijms17040550 - 20 Apr 2016

Cited by 22 | Viewed by 9698

Abstract

Magnetic isolation of biological targets is in major demand in the biotechnology industry today. This study considers the interaction of four surface-modified magnetic micro- and nanoparticles with selected DNA fragments. Different surface modifications of nanomaghemite precursors were investigated: MAN37 (silica-coated), MAN127 (polyvinylpyrrolidone-coated), MAN158 [...] Read more.

Magnetic isolation of biological targets is in major demand in the biotechnology industry today. This study considers the interaction of four surface-modified magnetic micro- and nanoparticles with selected DNA fragments. Different surface modifications of nanomaghemite precursors were investigated: MAN37 (silica-coated), MAN127 (polyvinylpyrrolidone-coated), MAN158 (phosphate-coated), and MAN164 (tripolyphosphate-coated). All particles were positive polycharged agglomerated monodispersed systems. Mean particle sizes were 0.48, 2.97, 2.93, and 3.67 μm for MAN37, MAN127, MAN164, and MAN158, respectively. DNA fragments exhibited negative zeta potential of −0.22 mV under binding conditions (high ionic strength, low pH, and dehydration). A decrease in zeta potential of particles upon exposure to DNA was observed with exception of MAN158 particles. The measured particle size of MAN164 particles increased by nearly twofold upon exposure to DNA. Quantitative PCR isolation of DNA with a high retrieval rate was observed by magnetic particles MAN127 and MAN164. Interaction between polycharged magnetic particles and DNA is mediated by various binding mechanisms such as hydrophobic and electrostatic interactions. Future development of DNA isolation technology requires an understanding of the physical and biochemical conditions of this process. Full article

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A RNA-DNA Hybrid Aptamer for Nanoparticle-Based Prostate Tumor Targeted Drug Delivery

by John C. Leach, Andrew Wang, Kaiming Ye and Sha Jin

Int. J. Mol. Sci. 2016, 17(3), 380; https://doi.org/10.3390/ijms17030380 - 14 Mar 2016

Cited by 52 | Viewed by 8454

Abstract

The side effects of radio- and chemo-therapy pose long-term challenges on a cancer patient’s health. It is, therefore, highly desirable to develop more effective therapies that can specifically target carcinoma cells without damaging normal and healthy cells. Tremendous efforts have been made in [...] Read more.

The side effects of radio- and chemo-therapy pose long-term challenges on a cancer patient’s health. It is, therefore, highly desirable to develop more effective therapies that can specifically target carcinoma cells without damaging normal and healthy cells. Tremendous efforts have been made in the past to develop targeted drug delivery systems for solid cancer treatment. In this study, a new aptamer, A10-3-J1, which recognizes the extracellular domain of the prostate specific membrane antigen (PSMA), was designed. A super paramagnetic iron oxide nanoparticle-aptamer-doxorubicin (SPIO-Apt-Dox) was fabricated and employed as a targeted drug delivery platform for cancer therapy. This DNA RNA hybridized aptamer antitumor agent was able to enhance the cytotoxicity of targeted cells while minimizing collateral damage to non-targeted cells. This SPIO-Apt-Dox nanoparticle has specificity to PSMA⁺ prostate cancer cells. Aptamer inhibited nonspecific uptake of membrane-permeable doxorubic to the non-target cells, leading to reduced untargeted cytotoxicity and endocytic uptake while enhancing targeted cytotoxicity and endocytic uptake. The experimental results indicate that the drug delivery platform can yield statistically significant effectiveness being more cytotoxic to the targeted cells as opposed to the non-targeted cells. Full article

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Evaluation of the Cytotoxic Behavior of Fungal Extracellular Synthesized Ag Nanoparticles Using Confocal Laser Scanning Microscope

by Taher A. Salaheldin, Sherif M. Husseiny, Abdullah M. Al-Enizi, Ahmed Elzatahry and Alan H. Cowley

Int. J. Mol. Sci. 2016, 17(3), 329; https://doi.org/10.3390/ijms17030329 - 3 Mar 2016

Cited by 21 | Viewed by 6739

Abstract

Silver nanoparticles have been synthesized by subjecting a reaction medium to a Fusarium oxysporum biomass at 28 °C for 96 h. The biosynthesized Ag nanoparticles were characterized on the basis of their anticipated peak at 405 nm using UV-Vis-NIR spectroscopy. Structural confirmation was [...] Read more.

Silver nanoparticles have been synthesized by subjecting a reaction medium to a Fusarium oxysporum biomass at 28 °C for 96 h. The biosynthesized Ag nanoparticles were characterized on the basis of their anticipated peak at 405 nm using UV-Vis-NIR spectroscopy. Structural confirmation was evident from the characteristic X-ray diffraction (XRD) pattern, high-resolution transmission electron Microscopy (HRTEM) and the particle size analyzer. The Ag nanoparticles were of dimension 40 ± 5 nm and spherical in shape. The study mainly focused on using the confocal laser scanning microscope (CLSM) to examine the cytotoxic activities of fungal synthesized Ag nanoparticles on a human breast carcinoma cell line MCF7 cell, which featured remarkable vacuolation, thus indicating a potent cytotoxic activity. Full article

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Silica Nanoparticles Induce Oxidative Stress and Autophagy but Not Apoptosis in the MRC-5 Cell Line

by Sorina Nicoleta Petrache Voicu, Diana Dinu, Cornelia Sima, Anca Hermenean, Aurel Ardelean, Elena Codrici, Miruna Silvia Stan, Otilia Zărnescu and Anca Dinischiotu

Int. J. Mol. Sci. 2015, 16(12), 29398-29416; https://doi.org/10.3390/ijms161226171 - 10 Dec 2015

Cited by 93 | Viewed by 8527

Abstract

This study evaluated the in vitro effects of 62.5 µg/mL silica nanoparticles (SiO₂ NPs) on MRC-5 human lung fibroblast cells for 24, 48 and 72 h. The nanoparticles’ morphology, composition, and structure were investigated using high resolution transmission electron microscopy, selected area [...] Read more.

This study evaluated the in vitro effects of 62.5 µg/mL silica nanoparticles (SiO₂ NPs) on MRC-5 human lung fibroblast cells for 24, 48 and 72 h. The nanoparticles’ morphology, composition, and structure were investigated using high resolution transmission electron microscopy, selected area electron diffraction and X-ray diffraction. Our study showed a decreased cell viability and the induction of cellular oxidative stress as evidenced by an increased level of reactive oxygen species (ROS), carbonyl groups, and advanced oxidation protein products after 24, 48, and 72 h, as well as a decreased concentration of glutathione (GSH) and protein sulfhydryl groups. The protein expression of Hsp27, Hsp60, and Hsp90 decreased at all time intervals, while the level of protein Hsp70 remained unchanged during the exposure. Similarly, the expression of p53, MDM2 and Bcl-2 was significantly decreased for all time intervals, while the expression of Bax, a marker for apoptosis, was insignificantly downregulated. These results correlated with the increase of pro-caspase 3 expression. The role of autophagy in cellular response to SiO₂ NPs was demonstrated by a fluorescence-labeled method and by an increased level of LC3-II/LC3-I ratio. Taken together, our data suggested that SiO₂ NPs induced ROS-mediated autophagy in MRC-5 cells as a possible mechanism of cell survival. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Intravenous Administration of Cilostazol Nanoparticles Ameliorates Acute Ischemic Stroke in a Cerebral Ischemia/Reperfusion-Induced Injury Model

by Noriaki Nagai, Chiaki Yoshioka, Yoshimasa Ito, Yoshinori Funakami, Hiroyuki Nishikawa and Atsufumi Kawabata

Int. J. Mol. Sci. 2015, 16(12), 29329-29344; https://doi.org/10.3390/ijms161226166 - 9 Dec 2015

Cited by 36 | Viewed by 7268

Abstract

It was reported that cilostazol (CLZ) suppressed disruption of the microvasculature in ischemic areas. In this study, we have designed novel injection formulations containing CLZ nanoparticles using 0.5% methylcellulose, 0.2% docusate sodium salt, and mill methods (CLZ_nano dispersion; particle size 81 ± [...] Read more.

It was reported that cilostazol (CLZ) suppressed disruption of the microvasculature in ischemic areas. In this study, we have designed novel injection formulations containing CLZ nanoparticles using 0.5% methylcellulose, 0.2% docusate sodium salt, and mill methods (CLZ_nano dispersion; particle size 81 ± 59 nm, mean ± S.D.), and investigated their toxicity and usefulness in a cerebral ischemia/reperfusion-induced injury model (MCAO/reperfusion mice). The pharmacokinetics of injections of CLZ_nano dispersions is similar to that of CLZ solutions prepared with 2-hydroxypropyl-β-cyclodextrin, and no changes in the rate of hemolysis of rabbit red blood cells, a model of cell injury, were observed with CLZ_nano dispersions. In addition, the intravenous injection of 0.6 mg/kg CLZ_nano dispersions does not affect the blood pressure and blood flow, and the 0.6 mg/kg CLZ_nano dispersions ameliorate neurological deficits and ischemic stroke in MCAO/reperfusion mice. It is possible that the CLZ_nano dispersions will provide effective therapy for ischemic stroke patients, and that injection preparations of lipophilic drugs containing drug nanoparticles expand their therapeutic usage. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Effects of Monotypic and Binary Mixtures of Metal Oxide Nanoparticles on Microbial Growth in Sandy Soil Collected from Artificial Recharge Sites

by Kyung-Seok Ko, Kyoochul Ha and In Chul Kong

Int. J. Mol. Sci. 2015, 16(11), 27967-27977; https://doi.org/10.3390/ijms161126066 - 24 Nov 2015

Cited by 7 | Viewed by 5640

Abstract

The potential effects of monotypic and binary metal oxide nanoparticles (NPs, ZnO, NiO, Co₃O₄ and TiO₂) on microbial growth were evaluated in sandy soil collected from artificial recharge sites. Microbial growth was assessed based on adenosine triphosphate (ATP) [...] Read more.

The potential effects of monotypic and binary metal oxide nanoparticles (NPs, ZnO, NiO, Co₃O₄ and TiO₂) on microbial growth were evaluated in sandy soil collected from artificial recharge sites. Microbial growth was assessed based on adenosine triphosphate (ATP) content, dehydrogenase activity (DHA), and viable cell counts (VCC). Microbial growth based on ATP content and VCC showed considerable differences depending on NP type and concentration, whereas DHA did not significantly change. In general, ZnO NPs showed the strongest effect on microbial growth in all measurements, showing an EC₅₀ value of 10.9 mg/L for ATP content. The ranking (EC₅₀) of NPs based on their effect on microbial growth assessed by ATP content and VCC was ZnO > Co₃O₄ > NiO > TiO₂. Upon exposure to binary NP mixtures, synergistic and additive modes of action were observed for ATP content and VCC, respectively. The ranges of observed (P(O)) and expected (P(E)) activity were 83%–92% and 78%–82% of the control (p-value 0.0010) based on ATP content and 78%–95% and 72%–94% of the control (p-value 0.8813) based on VCC under the tested conditions, respectively. The results indicate that the effects of NP mixtures on microbial growth in the sandy soil matrix were as great, or greater, than those of single NPs. Therefore, understanding the effects of single NPs and NP mixtures is essential for proper ecological risk assessment. Additionally, these findings demonstrate that the evaluation of NP effects may be profoundly influenced by the method of microbial growth measurement. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Safety Profile of TiO₂-Based Photocatalytic Nanofabrics for Indoor Formaldehyde Degradation

by Guixin Cui, Yan Xin, Xin Jiang, Mengqi Dong, Junling Li, Peng Wang, Shumei Zhai, Yongchun Dong, Jianbo Jia and Bing Yan

Int. J. Mol. Sci. 2015, 16(11), 27721-27729; https://doi.org/10.3390/ijms161126055 - 19 Nov 2015

Cited by 14 | Viewed by 6621

Abstract

Anatase TiO₂ nanoparticles (TNPs) are synthesized using the sol-gel method and loaded onto the surface of polyester-cotton (65/35) fabrics. The nanofabrics degrade formaldehyde at an efficiency of 77% in eight hours with visible light irradiation or 97% with UV light. The loaded [...] Read more.

Anatase TiO₂ nanoparticles (TNPs) are synthesized using the sol-gel method and loaded onto the surface of polyester-cotton (65/35) fabrics. The nanofabrics degrade formaldehyde at an efficiency of 77% in eight hours with visible light irradiation or 97% with UV light. The loaded TNPs display very little release from nanofabrics (~0.0%) during a standard fastness to rubbing test. Assuming TNPs may fall off nanofabrics during their life cycles, we also examine the possible toxicity of TNPs to human cells. We found that up to a concentration of 220 μg/mL, they do not affect viability of human acute monocytic leukemia cell line THP-1 macrophages and human liver and kidney cells. Full article

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Pooling and Analysis of Published in Vitro Data: A Proof of Concept Study for the Grouping of Nanoparticles

by Myrtill Simkó, Sonja Tischler and Mats-Olof Mattsson

Int. J. Mol. Sci. 2015, 16(11), 26211-26236; https://doi.org/10.3390/ijms161125954 - 2 Nov 2015

Cited by 10 | Viewed by 6752

Abstract

The study aim was to test the applicability of pooling of nanomaterials-induced in vitro data for identifying the toxic capacity of specific (SiO₂, TiO₂, ZnO, CuO, CeO₂ and carbon nanotubes, [CNT]) nanoparticles (NP) and to test the usefulness [...] Read more.

The study aim was to test the applicability of pooling of nanomaterials-induced in vitro data for identifying the toxic capacity of specific (SiO₂, TiO₂, ZnO, CuO, CeO₂ and carbon nanotubes, [CNT]) nanoparticles (NP) and to test the usefulness for grouping purposes. Publication selection was based on specific criteria regarding experimental conditions. Two relevant biological endpoints were selected; generation of intracellular reactive oxygen species (ROS) and viability above 90%. The correlations of the ROS ratios with the NP parameters’ size, concentration, and exposure time were analysed. The obtained data sets were then analysed with multiple regression analysis of variance (ANOVA) and the Tukey post-hoc test. The results show that this method is applicable for the selected metal oxide NP, but might need reconsideration and a larger data set for CNT. Several statistically significant correlations and results were obtained, thus validating the method. Furthermore, the relevance of the combination of ROS release with a cell viability test was shown. The data also show that it is advisable to compare ROS production of professional phagocytic with non-phagocytic cells. In conclusion, this is the first systematic analysis showing that pooling of available data into groups is a useful method for evaluation of data regarding NP induced toxicity in vitro. Full article

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Graphene Functionalized with Arginine Decreases the Development of Glioblastoma Multiforme Tumor in a Gene-Dependent Manner

by Ewa Sawosz, Sławomir Jaworski, Marta Kutwin, Krishna Prasad Vadalasetty, Marta Grodzik, Mateusz Wierzbicki, Natalia Kurantowicz, Barbara Strojny, Anna Hotowy, Ludwika Lipińska, Joanna Jagiełło and André Chwalibog

Int. J. Mol. Sci. 2015, 16(10), 25214-25233; https://doi.org/10.3390/ijms161025214 - 23 Oct 2015

Cited by 36 | Viewed by 7620

Abstract

Our previous studies revealed that graphene had anticancer properties in experiments in vitro with glioblastoma multiforme (GBM) cells and in tumors cultured in vivo. We hypothesized that the addition of arginine or proline to graphene solutions might counteract graphene agglomeration and increase the [...] Read more.

Our previous studies revealed that graphene had anticancer properties in experiments in vitro with glioblastoma multiforme (GBM) cells and in tumors cultured in vivo. We hypothesized that the addition of arginine or proline to graphene solutions might counteract graphene agglomeration and increase the activity of graphene. Experiments were performed in vitro with GBM U87 cells and in vivo with GBM tumors cultured on chicken embryo chorioallantoic membranes. The measurements included cell morphology, mortality, viability, tumor morphology, histology, and gene expression. The cells and tumors were treated with reduced graphene oxide (rGO) and rGO functionalized with arginine (rGO + Arg) or proline (rGO + Pro). The results confirmed the anticancer effect of graphene on GBM cells and tumor tissue. After functionalization with amino acids, nanoparticles were distributed more specifically, and the flakes of graphene were less agglomerated. The molecule of rGO + Arg did not increase the expression of TP53 in comparison to rGO, but did not increase the expression of MDM2 or the MDM2/TP53 ratio in the tumor, suggesting that arginine may block MDM2 expression. The expression of NQO1, known to be a strong protector of p53 protein in tumor tissue, was greatly increased. The results indicate that the complex of rGO + Arg has potential in GBM therapy. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Staphylococcus aureus and MRSA Growth and Biofilm Formation after Treatment with Antibiotics and SeNPs

by Kristyna Cihalova, Dagmar Chudobova, Petr Michalek, Amitava Moulick, Roman Guran, Pavel Kopel, Vojtech Adam and Rene Kizek

Int. J. Mol. Sci. 2015, 16(10), 24656-24672; https://doi.org/10.3390/ijms161024656 - 16 Oct 2015

Cited by 70 | Viewed by 11064

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a dangerous pathogen resistant to β-lactam antibiotics. Due to its resistance, it is difficult to manage the infections caused by this strain. We examined this issue in terms of observation of the growth properties and ability to form [...] Read more.

Methicillin-resistant Staphylococcus aureus (MRSA) is a dangerous pathogen resistant to β-lactam antibiotics. Due to its resistance, it is difficult to manage the infections caused by this strain. We examined this issue in terms of observation of the growth properties and ability to form biofilms in sensitive S. aureus and MRSA after the application of antibiotics (ATBs)—ampicillin, oxacillin and penicillin—and complexes of selenium nanoparticles (SeNPs) with these ATBs. The results suggest the strong inhibition effect of SeNPs in complexes with conventional ATBs. Using the impedance method, a higher disruption of biofilms was observed after the application of ATB complexes with SeNPs compared to the group exposed to ATBs without SeNPs. The biofilm formation was intensely inhibited (up to 99% ± 7% for S. aureus and up to 94% ± 4% for MRSA) after application of SeNPs in comparison with bacteria without antibacterial compounds whereas ATBs without SeNPs inhibited S. aureus up to 79% ± 5% and MRSA up to 16% ± 2% only. The obtained results provide a basis for the use of SeNPs as a tool for the treatment of bacterial infections, which can be complicated because of increasing resistance of bacteria to conventional ATB drugs. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Structural Analysis of Crystalline R(+)-α-Lipoic Acid-α-cyclodextrin Complex Based on Microscopic and Spectroscopic Studies

by Naoko Ikuta, Takatsugu Endo, Shota Hosomi, Keita Setou, Shiori Tanaka, Noriko Ogawa, Hiromitsu Yamamoto, Tomoyuki Mizukami, Shoji Arai, Masayuki Okuno, Kenji Takahashi, Keiji Terao and Seiichi Matsugo

Int. J. Mol. Sci. 2015, 16(10), 24614-24628; https://doi.org/10.3390/ijms161024614 - 16 Oct 2015

Cited by 12 | Viewed by 7282

Abstract

R(+)-α-lipoic acid (RALA) is a naturally-occurring substance, and its protein-bound form plays significant role in the energy metabolism in the mitochondria. RALA is vulnerable to a variety of physical stimuli, including heat and UV light, which prompted us to study the stability [...] Read more.

R(+)-α-lipoic acid (RALA) is a naturally-occurring substance, and its protein-bound form plays significant role in the energy metabolism in the mitochondria. RALA is vulnerable to a variety of physical stimuli, including heat and UV light, which prompted us to study the stability of its complexes with cyclodextrins (CDs). In this study, we have prepared and purified a crystalline RALA-αCD complex and evaluated its properties in the solid state. The results of ¹H NMR and PXRD analyses indicated that the crystalline RALA-αCD complex is a channel type complex with a molar ratio of 2:3 (RALA:α-CD). Attenuated total reflection/Fourier transform infrared analysis of the complex showed the shift of the C=O stretching vibration of RALA due to the formation of the RALA-αCD complex. Raman spectroscopic analysis revealed the significant weakness of the S–S and C–S stretching vibrations of RALA in the RALA-αCD complex implying that the dithiolane ring of RALA is almost enclosed in glucose ring of α-CD. Extent of this effect was dependent on the direction of the excitation laser to the hexagonal morphology of the crystal. Solid-state NMR analysis allowed for the chemical shift of the C=O peak to be precisely determined. These results suggested that RALA was positioned in the α-CD cavity with its 1,2-dithiolane ring orientated perpendicular to the plane of the α-CD ring. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Open AccessArticle

Liver Toxicity of Cadmium Telluride Quantum Dots (CdTe QDs) Due to Oxidative Stress in Vitro and in Vivo

by Ting Zhang, Yuanyuan Hu, Meng Tang, Lu Kong, Jiali Ying, Tianshu Wu, Yuying Xue and Yuepu Pu

Int. J. Mol. Sci. 2015, 16(10), 23279-23299; https://doi.org/10.3390/ijms161023279 - 25 Sep 2015

Cited by 87 | Viewed by 8531

Abstract

With the applications of quantum dots (QDs) expanding, many studies have described the potential adverse effects of QDs, yet little attention has been paid to potential toxicity of QDs in the liver. The aim of this study was to investigate the effects of [...] Read more.

With the applications of quantum dots (QDs) expanding, many studies have described the potential adverse effects of QDs, yet little attention has been paid to potential toxicity of QDs in the liver. The aim of this study was to investigate the effects of cadmium telluride (CdTe) QDs in mice and murine hepatoma cells alpha mouse liver 12 (AML 12). CdTe QDs administration significantly increased the level of lipid peroxides marker malondialdehyde (MDA) in the livers of treated mice. Furthermore, CdTe QDs caused cytotoxicity in AML 12 cells in a dose- and time-dependent manner, which was likely mediated through the generation of reactive oxygen species (ROS) and the induction of apoptosis. An increase in ROS generation with a concomitant increase in the gene expression of the tumor suppressor gene p53, the pro-apoptotic gene Bcl-2 and a decrease in the anti-apoptosis gene Bax, suggested that a mitochondria mediated pathway was involved in CdTe QDs’ induced apoptosis. Finally, we showed that NF-E2-related factor 2 (Nrf2) deficiency blocked induced oxidative stress to protect cells from injury induced by CdTe QDs. These findings provide insights into the regulatory mechanisms involved in the activation of Nrf2 signaling that confers protection against CdTe QDs-induced apoptosis in hepatocytes. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Open AccessArticle

Attenuation of Combined Nickel(II) Oxide and Manganese(II, III) Oxide Nanoparticles’ Adverse Effects with a Complex of Bioprotectors

by Ilzira A. Minigalieva, Boris A. Katsnelson, Larisa I. Privalova, Marina P. Sutunkova, Vladimir B. Gurvich, Vladimir Y. Shur, Ekaterina V. Shishkina, Irene E. Valamina, Oleg H. Makeyev, Vladimir G. Panov, Anatoly N. Varaksin, Ekaterina V. Grigoryeva and Ekaterina Y. Meshtcheryakova

Int. J. Mol. Sci. 2015, 16(9), 22555-22583; https://doi.org/10.3390/ijms160922555 - 17 Sep 2015

Cited by 50 | Viewed by 7395

Abstract

Stable suspensions of NiO and Mn₃O₄ nanoparticles (NPs) with a mean (±s.d.) diameter of 16.7 ± 8.2 and 18.4 ± 5.4 nm, respectively, purposefully prepared by laser ablation of 99.99% pure nickel or manganese in de-ionized water, were repeatedly injected [...] Read more.

Stable suspensions of NiO and Mn₃O₄ nanoparticles (NPs) with a mean (±s.d.) diameter of 16.7 ± 8.2 and 18.4 ± 5.4 nm, respectively, purposefully prepared by laser ablation of 99.99% pure nickel or manganese in de-ionized water, were repeatedly injected intraperitoneally (IP) to rats at a dose of 2.5 mg/kg 3 times a week up to 18 injections, either alone or in combination. A group of rats was injected with this combination with the background oral administration of a “bio-protective complex” (BPC) comprising pectin, vitamins A, C, E, glutamate, glycine, N-acetylcysteine, selenium, iodide and omega-3 PUFA, this composition having been chosen based on mechanistic considerations and previous experience. After the termination of injections, many functional and biochemical indices and histopathological features (with morphometric assessment) of the liver, spleen, kidneys and brain were evaluated for signs of toxicity. The Ni and Mn content of these organs was measured with the help of the atomic emission and electron paramagnetic resonance spectroscopies. We obtained blood leukocytes for performing the RAPD (Random Amplified Polymorphic DNA) test. Although both metallic NPs proved adversely bio-active in many respects considered in this study, Mn₃O₄-NPswere somewhat more noxious than NiO-NPs as concerns most of the non-specific toxicity manifestations and they induced more marked damage to neurons in the striatum and the hippocampus, which may be considered an experimental correlate of the manganese-induced Parkinsonism. The comparative solubility of the Mn₃O₄-NPs and NiO-NPs in a biological medium is discussed as one of the factors underlying the difference in their toxicokinetics and toxicities. The BPC has attenuated both the organ-systemic toxicity and the genotoxicity of Mn₃O₄-NPs in combination with NiO-NPs. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Influence of Parathyroid Hormone-Loaded PLGA Nanoparticles in Porous Scaffolds for Bone Regeneration

by Piergiorgio Gentile, Vijay Kumar Nandagiri, Ritesh Pabari, Jacqueline Daly, Chiara Tonda-Turo, Gianluca Ciardelli and Zebunnissa Ramtoola

Int. J. Mol. Sci. 2015, 16(9), 20492-20510; https://doi.org/10.3390/ijms160920492 - 28 Aug 2015

Cited by 29 | Viewed by 6435

Abstract

Biodegradable poly(lactide-co-glycolide) (PLGA) nanoparticles, containing human parathyroid hormone (PTH (1–34)), prepared by a modified double emulsion-solvent diffusion-evaporation method, were incorporated in porous freeze-dried chitosan-gelatin (CH-G) scaffolds. The PTH-loaded nanoparticles (NPTH) were characterised in terms of morphology, size, protein loading, release kinetics [...] Read more.

Biodegradable poly(lactide-co-glycolide) (PLGA) nanoparticles, containing human parathyroid hormone (PTH (1–34)), prepared by a modified double emulsion-solvent diffusion-evaporation method, were incorporated in porous freeze-dried chitosan-gelatin (CH-G) scaffolds. The PTH-loaded nanoparticles (NPTH) were characterised in terms of morphology, size, protein loading, release kinetics and in vitro assessment of biological activity of released PTH and cytocompatibility studies against clonal human osteoblast (hFOB) cells. Structural integrity of incorporated and released PTH from nanoparticles was found to be intact by using Tris-tricine SDS-PAGE. In vitro PTH release kinetics from PLGA nanoparticles were characterised by a burst release followed by a slow release phase for 3–4 weeks. The released PTH was biologically active as evidenced by the stimulated release of cyclic AMP from hFOB cells as well as increased mineralisation studies. in vitro and cell studies demonstrated that the PTH bioactivity was maintained during the fabrication of PLGA nanoparticles and upon release. Finally, a content of 33.3% w/w NPTHs was incorporated in CH-G scaffolds, showing an intermittent release during the first 10 days and, followed by a controlled release over 28 days of observation time. The increased expression of Alkaline Phosphatase levels on hFOB cells further confirmed the activity of intermittently released PTH from scaffolds. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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New Hybrid Nanomaterial Based on Self-Assembly of Cyclodextrins and Cobalt Prussian Blue Analogue Nanocubes

by Caio L. C. Carvalho, Anna T. B. Silva, Lucyano J. A. Macedo, Roberto A. S. Luz, José M. Moita Neto, Ubirajara P. Rodrigues Filho and Welter Cantanhêde

Int. J. Mol. Sci. 2015, 16(7), 14594-14607; https://doi.org/10.3390/ijms160714594 - 29 Jun 2015

Cited by 18 | Viewed by 7924

Abstract

Supramolecular self-assembly has been demonstrated to be a useful approach to developing new functional nanomaterials. In this work, we used a cobalt Prussian blue analogue (PBA, Co₃[Co(CN)₆]₂) compound and a β-cyclodextrin (CD) macrocycle to develop a novel [...] Read more.

Supramolecular self-assembly has been demonstrated to be a useful approach to developing new functional nanomaterials. In this work, we used a cobalt Prussian blue analogue (PBA, Co₃[Co(CN)₆]₂) compound and a β-cyclodextrin (CD) macrocycle to develop a novel host-guest PBA-CD nanomaterial. The preparation of the functional magnetic material involved the self-assembly of CD molecules onto a PBA surface by a co-precipitation method. According to transmission electronic microscopy results, PBA-CD exhibited a polydisperse structure composed of 3D nanocubes with a mean edge length of 85 nm, which became shorter after CD incorporation. The supramolecular arrangement and structural, crystalline and thermal properties of the hybrid material were studied in detail by vibrational and electronic spectroscopies and X-ray diffraction. The cyclic voltammogram of the hybrid material in a 0.1 mol·L⁻¹ NaCl supporting electrolyte exhibited a quasi-reversible redox process, attributed to Co²⁺/Co³⁺ conversion, with an E_1/2 value of 0.46 V (vs. SCE), with higher reversibility observed for the system in the presence of CD. The standard rate constants for PBA and PBA-CD were determined to be 0.07 and 0.13 s⁻¹, respectively, which suggests that the interaction between the nanocubes and CD at the supramolecular level improves electron transfer. We expect that the properties observed for the hybrid material make it a potential candidate for (bio)sensing designs with a desirable capability for drug delivery. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Microwave-Assisted Synthesis of Glutathione-Capped CdTe/CdSe Near-Infrared Quantum Dots for Cell Imaging

by Xiaogang Chen, Liang Li, Yongxian Lai, Jianna Yan, Yichen Tang and Xiuli Wang

Int. J. Mol. Sci. 2015, 16(5), 11500-11508; https://doi.org/10.3390/ijms160511500 - 19 May 2015

Cited by 23 | Viewed by 7490

Abstract

These glutathione (GSH)-conjugated CdTe/CdSe core/shell quantum dot (QD) nanoparticles in aqueous solution were synthesized using a microwave-assisted approach. The prepared type II core/shell QD nanoparticles were characterized by UV–Vis absorption, photoluminescence (PL) spectroscopy, X-ray powder diffraction (XRD) and high-resolution transmission electron microscopy (HR-TEM). [...] Read more.

These glutathione (GSH)-conjugated CdTe/CdSe core/shell quantum dot (QD) nanoparticles in aqueous solution were synthesized using a microwave-assisted approach. The prepared type II core/shell QD nanoparticles were characterized by UV–Vis absorption, photoluminescence (PL) spectroscopy, X-ray powder diffraction (XRD) and high-resolution transmission electron microscopy (HR-TEM). Results revealed that the QD nanoparticles exhibited good dispersity, a uniform size distribution and tunable fluorescence emission in the near-infrared (NIR) region. In addition, these nanoparticles exhibited good biocompatibility and photoluminescence in cell imaging. In particular, this type of core/shell NIR QDs may have potential applications in molecular imaging. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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In Ovo Administration of Silver Nanoparticles and/or Amino Acids Influence Metabolism and Immune Gene Expression in Chicken Embryos

by Subrat K. Bhanja, Anna Hotowy, Manish Mehra, Ewa Sawosz, Lane Pineda, Krishna Prasad Vadalasetty, Natalia Kurantowicz and André Chwalibog

Int. J. Mol. Sci. 2015, 16(5), 9484-9503; https://doi.org/10.3390/ijms16059484 - 27 Apr 2015

Cited by 49 | Viewed by 7915

Abstract

Due to their physicochemical and biological properties, silver nanoparticles (NanoAg) have a wide range of applications. In the present study, their roles as a carrier of nutrients and an immunomodulator were tested in chicken embryos. Cysteine (Cys)+NanoAg injected embryos had smaller livers but [...] Read more.

Due to their physicochemical and biological properties, silver nanoparticles (NanoAg) have a wide range of applications. In the present study, their roles as a carrier of nutrients and an immunomodulator were tested in chicken embryos. Cysteine (Cys)+NanoAg injected embryos had smaller livers but heavier breasts on the 19th day of embryogenesis. Cys injected embryos had lower oxygen consumption compared to threonine (Thr) or NanoAg injected embryos. The energy expenditure in Thr+NanoAg, or NanoAg injected embryos was higher than Cys or Cys+NanoAg but was not different from uninjected control embryos. Relative expression of the hepatic insulin-like growth factor-I (IGF-I) gene was higher in Cys or NanoAg injected embryos after lipopolysaccharide (LPS) induction. The gene expression of hepatic tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) did not differ among amino acids, NanoAg and uninjected controls in the non-LPS groups, but increased by many folds in the LPS treated NanoAg, Cys and Cys+NanoAg groups. In LPS treated spleens, TNF-α expression was also up-regulated by NanoAg, amino acids and their combinations, but interleukin-10 (IL-10) expression was down-regulated in Thr, Cys or Thr+NanoAg injected embryos. Toll like receptor-2 (TLR2) expression did not differ in NanoAg or amino acids injected embryos; however, toll like receptor-4 (TLR4) expression was higher in all treated embryos, except for Cys+NanoAg, than in uninjected control embryos. We concluded that NanoAg either alone or in combination with amino acids did not affect embryonic growth but improved immunocompetence, indicating that NanoAg and amino acid complexes can act as potential agents for the enhancement of innate and adaptive immunity in chicken. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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In Vitro Cytotoxic Evaluation of MgO Nanoparticles and Their Effect on the Expression of ROS Genes

by Rangarajulu Senthil Kumaran, Yong-Keun Choi, Vijay Singh, Hak-Jin Song, Kyung-Guen Song, Kwang Jin Kim and Hyung Joo Kim

Int. J. Mol. Sci. 2015, 16(4), 7551-7564; https://doi.org/10.3390/ijms16047551 - 3 Apr 2015

Cited by 43 | Viewed by 6567

Abstract

Water-dispersible MgO nanoparticles were tested to investigate their cytotoxic effects on oxidative stress gene expression. In this in vitro study, genes related to reactive oxygen species (ROS), glutathione S-transferase (GST) and catalase, were quantified using real-time polymerase chain reactions (molecular level) and [...] Read more.

Water-dispersible MgO nanoparticles were tested to investigate their cytotoxic effects on oxidative stress gene expression. In this in vitro study, genes related to reactive oxygen species (ROS), glutathione S-transferase (GST) and catalase, were quantified using real-time polymerase chain reactions (molecular level) and molecular beacon technologies (cellular level). The monodispersed MgO nanoparticles, 20 nm in size, were used to treat human cancer cell lines (liver cancer epithelial cells) at different concentrations (25, 75 and 150 µg/mL) and incubation times (24, 48 and 72 h). Both the genetic and cellular cytotoxic screening methods produced consistent results, showing that GST and catalase ROS gene expression was maximized at 150 µg/mL nanoparticle treatment with 48 h incubation. However, the genotoxic effect of MgO nanoparticles was not significant compared with control experiments, which indicates its significant potential applications in nanomedicine as a diagnostic and therapeutic tool. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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In Vitro Investigation of Self-Assembled Nanoparticles Based on Hyaluronic Acid-Deoxycholic Acid Conjugates for Controlled Release Doxorubicin: Effect of Degree of Substitution of Deoxycholic Acid

by Wen-Hao Wei, Xue-Meng Dong and Chen-Guang Liu

Int. J. Mol. Sci. 2015, 16(4), 7195-7209; https://doi.org/10.3390/ijms16047195 - 31 Mar 2015

Cited by 27 | Viewed by 7498

Abstract

Self-assembled nanoparticles based on a hyaluronic acid-deoxycholic acid (HD) chemical conjugate with different degree of substitution (DS) of deoxycholic acid (DOCA) were prepared. The degree of substitution (DS) was determined by titration method. The nanoparticles were loaded with doxorubicin (DOX) as the model [...] Read more.

Self-assembled nanoparticles based on a hyaluronic acid-deoxycholic acid (HD) chemical conjugate with different degree of substitution (DS) of deoxycholic acid (DOCA) were prepared. The degree of substitution (DS) was determined by titration method. The nanoparticles were loaded with doxorubicin (DOX) as the model drug. The human cervical cancer (HeLa) cell line was utilized for in vitro studies and cell cytotoxicity of DOX incorporated in the HD nanoparticles was accessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, cellular uptake of fluorescently labeled nanoparticles was also investigated. An increase in the degree of deoxycholic acid substitution reduced the size of the nanoparticles and also enhanced their drug encapsulation efficiency (EE), which increased with the increase of DS. A higher degree of deoxycholic acid substitution also lead to a lower release rate and an initial burst release of doxorubicin from the nanoparticles. In summary, the degree of substitution allows the modulation of the particle size, drug encapsulation efficiency, drug release rate, and cell uptake efficiency of the nanoparticles. The herein developed hyaluronic acid-deoxycholic acid conjugates are a good candidate for drug delivery and could potentiate therapeutic formulations for doxorubicin–mediated cancer therapy. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Tumour Cell Membrane Poration and Ablation by Pulsed Low-Intensity Electric Field with Carbon Nanotubes

by Lijun Wang, Dun Liu, Ru Zhou, Zhigang Wang and Alfred Cuschieri

Int. J. Mol. Sci. 2015, 16(4), 6890-6901; https://doi.org/10.3390/ijms16046890 - 26 Mar 2015

Cited by 17 | Viewed by 6615

Abstract

Electroporation is a physical method to increase permeabilization of cell membrane by electrical pulses. Carbon nanotubes (CNTs) can potentially act like “lighting rods” or exhibit direct physical force on cell membrane under alternating electromagnetic fields thus reducing the required field strength. A cell [...] Read more.

Electroporation is a physical method to increase permeabilization of cell membrane by electrical pulses. Carbon nanotubes (CNTs) can potentially act like “lighting rods” or exhibit direct physical force on cell membrane under alternating electromagnetic fields thus reducing the required field strength. A cell poration/ablation system was built for exploring these effects of CNTs in which two-electrode sets were constructed and two perpendicular electric fields could be generated sequentially. By applying this system to breast cancer cells in the presence of multi-walled CNTs (MWCNTs), the effective pulse amplitude was reduced to 50 V/cm (main field)/15 V/cm (alignment field) at the optimized pulse frequency (5 Hz) of 500 pulses. Under these conditions instant cell membrane permeabilization was increased to 38.62%, 2.77-fold higher than that without CNTs. Moreover, we also observed irreversible electroporation occurred under these conditions, such that only 39.23% of the cells were viable 24 h post treatment, in contrast to 87.01% cell viability without presence of CNTs. These results indicate that CNT-enhanced electroporation has the potential for tumour cell ablation by significantly lower electric fields than that in conventional electroporation therapy thus avoiding potential risks associated with the use of high intensity electric pulses. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Nanoparticles of Copper Stimulate Angiogenesis at Systemic and Molecular Level

by Natalia Mroczek-Sosnowska, Ewa Sawosz, Krishna Prasad Vadalasetty, Monika Łukasiewicz, Jan Niemiec, Mateusz Wierzbicki, Marta Kutwin, Sławomir Jaworski and André Chwalibog

Int. J. Mol. Sci. 2015, 16(3), 4838-4849; https://doi.org/10.3390/ijms16034838 - 3 Mar 2015

Cited by 91 | Viewed by 7571

Abstract

Copper is a key element affecting blood vessel growth and muscle development. However, the ions released from Cu salts are toxic. Given their specific physicochemical properties, nanoparticles of Cu (NanoCu) may have different bioactivity and affect the development of blood vessel and muscles [...] Read more.

Copper is a key element affecting blood vessel growth and muscle development. However, the ions released from Cu salts are toxic. Given their specific physicochemical properties, nanoparticles of Cu (NanoCu) may have different bioactivity and affect the development of blood vessel and muscles in a different manner than Cu salts. The objective of the study was to evaluate the influence of NanoCu on embryo development and angiogenesis at the systemic and molecular level, in experiments using a chick embryo model. Fertilized chicken eggs were divided into a control group, and groups injected with a placebo, CuSO₄ or NanoCu. Embryo development at the whole body level and molecular indices using an embryo chorioallantoic membrane model were measured during embryogenesis. The present study indicated for the first time that NanoCu have pro-angiogenic properties at the systemic level, to a greater degree than CuSO₄ salt. The properties of NanoCu were confirmed at the molecular level, demonstrating significant effects on mRNA concentration and on mRNA gene expression of all pro-angiogenic and pro-proliferative genes measured herein. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Open AccessCommunication

Development of Biodegradable Nanocarriers Loaded with a Monoclonal Antibody

by Andrew Gdowski, Amalendu Ranjan, Anindita Mukerjee and Jamboor Vishwanatha

Int. J. Mol. Sci. 2015, 16(2), 3990-3995; https://doi.org/10.3390/ijms16023990 - 12 Feb 2015

Cited by 33 | Viewed by 7022

Abstract

Treatments utilizing monoclonal antibody therapeutics against intracellular protein-protein interactions in cancer cells have been hampered by several factors, including poor intracellular uptake and rapid lysosomal degradation. Our current work examines the feasibility of encapsulating monoclonal antibodies within poly(lactic-co-glycolic acid) (PLGA) nanoparticles [...] Read more.

Treatments utilizing monoclonal antibody therapeutics against intracellular protein-protein interactions in cancer cells have been hampered by several factors, including poor intracellular uptake and rapid lysosomal degradation. Our current work examines the feasibility of encapsulating monoclonal antibodies within poly(lactic-co-glycolic acid) (PLGA) nanoparticles using a water/oil/water double emulsion solvent evaporation technique. This method can be used to prepare protective polymeric nanoparticles for transporting functional antibodies to the cytoplasmic compartment of cancer cells. Nanoparticles were formulated and then characterized using a number of physical and biological parameters. The average nanoparticle size ranged from 221 to 252 nm with a low polydispersity index. Encapsulation efficiency of 16%–22% and antibody loading of 0.3%–1.12% were observed. The antibody molecules were released from the nanoparticles in a sustained manner and upon release maintained functionality. Our studies achieved successful formulation of antibody loaded polymeric nanoparticles, thus indicating that a PLGA-based antibody nanoformulation is a promising intracellular delivery vehicle for a large number of new intracellular antibody targets in cancer cells. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Multi-Walled Carbon Nanotubes Promote Cementoblast Differentiation and Mineralization through the TGF-β/Smad Signaling Pathway

by Lu Li, Zhimin Zhu, Weixiong Xiao and Lei Li

Int. J. Mol. Sci. 2015, 16(2), 3188-3201; https://doi.org/10.3390/ijms16023188 - 2 Feb 2015

Cited by 24 | Viewed by 6090

Abstract

Excretion of cementum by cementoblasts on the root surface is a process indispensable for the formation of a functional periodontal ligament. This study investigated whether carboxyl group-functionalized multi-walled carbon nanotubes (MWCNT-COOH) could enhance differentiation and mineralization of mammalian cementoblasts (OCCM-30) and the possible [...] Read more.

Excretion of cementum by cementoblasts on the root surface is a process indispensable for the formation of a functional periodontal ligament. This study investigated whether carboxyl group-functionalized multi-walled carbon nanotubes (MWCNT-COOH) could enhance differentiation and mineralization of mammalian cementoblasts (OCCM-30) and the possible signaling pathway involved in this process. Cementoblasts were incubated with various doses of MWCNT-COOH suspension. Cell viability was detected, and a scanning electron microscopy (SEM) observed both the nanomaterials and the growth of cells cultured with the materials. Alizarin red staining was used to investigate the formation of calcium deposits. Real-time PCR and western blot were used to detect cementoblast differentiation and the underlying mechanisms through the expression of the osteogenic genes and the downstream effectors of the TGF-β/Smad signaling. The results showed that 5 µg/mL MWCNT-COOH had the most obvious effects on promoting differentiation without significant toxicity. Alp, Ocn, Bsp, Opn, Col1 and Runx2 gene expression was up-regulated. Smad2 and Smad3 mRNA was up-regulated, while Smad7 was first down-regulated on Day 3 and later up-regulated on Day 7. The elevated levels of phospho-Smad2/3 were also confirmed by western blot. In sum, the MWCNT-COOH promoted cementoblast differentiation and mineralization, at least partially, through interactions with the TGF-β/Smad pathway. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Efficient Synthesis of a Maghemite/Gold Hybrid Nanoparticle System as a Magnetic Carrier for the Transport of Platinum-Based Metallotherapeutics

by Pavel Štarha, David Smola, Jiří Tuček and Zdeněk Trávníček

Int. J. Mol. Sci. 2015, 16(1), 2034-2051; https://doi.org/10.3390/ijms16012034 - 16 Jan 2015

Cited by 17 | Viewed by 9124

Abstract

The preparation and thorough characterization of a hybrid magnetic carrier system for the possible transport of activated platinum-based anticancer drugs, as demonstrated for cisplatin (cis-[Pt(NH₃)₂Cl₂], CDDP), are described. The final functionalized mag/Au–LA–CDDP* system consists of [...] Read more.

The preparation and thorough characterization of a hybrid magnetic carrier system for the possible transport of activated platinum-based anticancer drugs, as demonstrated for cisplatin (cis-[Pt(NH₃)₂Cl₂], CDDP), are described. The final functionalized mag/Au–LA–CDDP* system consists of maghemite/gold nanoparticles (mag/Au) coated by lipoic acid (HLA; LA stands for deprotonated form of lipoic acid) and functionalized by activated cisplatin in the form of cis-[Pt(NH₃)₂(H₂O)₂]²⁺ (CDDP*). The relevant techniques (XPS, EDS, ICP-MS) proved the incorporation of the platinum-containing species on the surface of the studied hybrid system. HRTEM, TEM and SEM images showed the nanoparticles as spherical with an average size of 12 nm, while their superparamagnetic feature was proven by ⁵⁷Fe Mössbauer spectroscopy. In the case of mag/Au, mag/Au–HLA and mag/Au–LA–CDDP*, weaker magnetic interactions among the Fe³⁺ centers of maghemite, as compared to maghemite nanoparticles (mag), were detected, which can be associated with the non-covalent coating of the maghemite surface by gold. The pH and time-dependent stability of the mag/Au–LA–CDDP* system in different media, represented by acetate (pH 5.0), phosphate (pH 7.0) and carbonate (pH 9.0) buffers and connected with the release of the platinum-containing species, showed the ability of CDDP* to be released from the functionalized nanosystem. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Open AccessArticle

Pulicaria glutinosa Extract: A Toolbox to Synthesize Highly Reduced Graphene Oxide-Silver Nanocomposites

by Abdulhadi H. Al-Marri, Mujeeb Khan, Merajuddin Khan, Syed F. Adil, Abdulrahman Al-Warthan, Hamad Z. Alkhathlan, Wolfgang Tremel, Joselito P. Labis, Mohammed Rafiq H. Siddiqui and Muhammad N. Tahir

Int. J. Mol. Sci. 2015, 16(1), 1131-1142; https://doi.org/10.3390/ijms16011131 - 5 Jan 2015

Cited by 55 | Viewed by 11330

Abstract

A green, one-step approach for the preparation of graphene/Ag nanocomposites (PE-HRG-Ag) via simultaneous reduction of both graphene oxide (GRO) and silver ions using Pulicaria glutinosa plant extract (PE) as reducing agent is reported. The plant extract functionalizes the surfaces of highly reduced graphene [...] Read more.

A green, one-step approach for the preparation of graphene/Ag nanocomposites (PE-HRG-Ag) via simultaneous reduction of both graphene oxide (GRO) and silver ions using Pulicaria glutinosa plant extract (PE) as reducing agent is reported. The plant extract functionalizes the surfaces of highly reduced graphene oxide (HRG) which helps in conjugating the Ag NPs to HRG. Increasing amounts of Ag precursor enhanced the density of Ag nanoparticles (NPs) on HRG. The preparation of PE-HRG-Ag nanocomposite is monitored by using ultraviolet–visible (UV-Vis) spectroscopy, powder X-ray diffraction (XRD), and energy dispersive X-ray (EDX). The as-prepared PE-HRG-Ag nanocomposities display excellent surface-enhanced Raman scattering (SERS) activity, and significantly increased the intensities of the Raman signal of graphene. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Open AccessArticle

Development and Application of a Label-Free Fluorescence Method for Determining the Composition of Gold Nanoparticle–Protein Conjugates

by Dmitriy V. Sotnikov, Anatoly V. Zherdev and Boris B. Dzantiev

Int. J. Mol. Sci. 2015, 16(1), 907-923; https://doi.org/10.3390/ijms16010907 - 31 Dec 2014

Cited by 28 | Viewed by 12235

Abstract

A method was developed for determining the composition of the conjugates between gold nanoparticles and proteins based on the intrinsic fluorescence of unbound protein molecules. The fluorescence was evaluated after separation of the conjugates from the reaction mixture by centrifugation. Gold nanoparticles obtained [...] Read more.

A method was developed for determining the composition of the conjugates between gold nanoparticles and proteins based on the intrinsic fluorescence of unbound protein molecules. The fluorescence was evaluated after separation of the conjugates from the reaction mixture by centrifugation. Gold nanoparticles obtained using the citrate technique (average diameter 24 nm) were conjugated at pH 5.4 with the following four proteins: human immunoglobulin G (IgG), bovine serum albumin (BSA), recombinant streptococcal protein G (protein G), and Kunitz-type soybean trypsin inhibitor (STI). The compositions of these conjugates were determined using the developed method. The conjugate compositions were dependent on the concentration of the added protein, and in all cases reached saturation. The equilibrium dissociation constants of the gold nanoparticle conjugates with IgG, BSA, protein G, STI in the initial section of the concentration dependence curve were 4, 6, 10, and 15 nM, respectively. Close to saturation, the corresponding values were 25, 76, 175, and 100 nM, respectively. The maximal binding capacities of a single gold nanoparticle for IgG, BSA, Protein G, and STI were 52, 90, 500, and 550, respectively, which agrees well with the hypothesis of monolayer immobilization. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Synergistic Effect of Bolus Exposure to Zinc Oxide Nanoparticles on Bleomycin-Induced Secretion of Pro-Fibrotic Cytokines without Lasting Fibrotic Changes in Murine Lungs

by Wenting Wu, Gaku Ichihara, Naozumi Hashimoto, Yoshinori Hasegawa, Yasuhiko Hayashi, Saeko Tada-Oikawa, Yuka Suzuki, Jie Chang, Masashi Kato, Corina N. D'Alessandro-Gabazza, Esteban C. Gabazza and Sahoko Ichihara

Int. J. Mol. Sci. 2015, 16(1), 660-676; https://doi.org/10.3390/ijms16010660 - 30 Dec 2014

Cited by 13 | Viewed by 7443

Abstract

Zinc oxide (ZnO) nanoparticles are widely used in various products, and the safety evaluation of this manufactured material is important. The present study investigated the inflammatory and fibrotic effects of pulmonary exposure to ZnO nanoparticles in a mouse model of pulmonary fibrosis. Pulmonary [...] Read more.

Zinc oxide (ZnO) nanoparticles are widely used in various products, and the safety evaluation of this manufactured material is important. The present study investigated the inflammatory and fibrotic effects of pulmonary exposure to ZnO nanoparticles in a mouse model of pulmonary fibrosis. Pulmonary fibrosis was induced by constant subcutaneous infusion of bleomycin (BLM). Female C57BL/6Jcl mice were divided into BLM-treated and non-treated groups. In each treatment group, 0, 10, 20 or 30 µg of ZnO nanoparticles were delivered into the lungs through pharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) and the lungs were sampled at Day 10 or 14 after administration. Pulmonary exposure by a single bolus of ZnO nanoparticles resulted in severe, but transient inflammatory infiltration and thickening of the alveolar septa in the lungs, along with the increase of total and differential cell counts in BLAF. The BALF level of interleukin (IL)-1β and transforming growth factor (TGF)-β was increased at Day 10 and 14, respectively. At Day 10, the synergistic effect of BLM and ZnO exposure was detected on IL-1β and monocyte chemotactic protein (MCP)-1 in BALF. The present study demonstrated the synergistic effect of pulmonary exposure to ZnO nanoparticles and subcutaneous infusion of BLM on the secretion of pro-fibrotic cytokines in the lungs. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Systemic Delivery of Protein Nanocages Bearing CTT Peptides for Enhanced Imaging of MMP-2 Expression in Metastatic Tumor Models

by Takahito Kawano, Masaharu Murata, Jing Shu Piao, Sayoko Narahara, Nobuhito Hamano, Jeong-Hun Kang and Makoto Hashizume

Int. J. Mol. Sci. 2015, 16(1), 148-158; https://doi.org/10.3390/ijms16010148 - 24 Dec 2014

Cited by 21 | Viewed by 6867

Abstract

Matrix metalloproteinase 2 (MMP-2) in metastatic cancer tissue, which is associated with a poor prognosis, is a potential target for tumor imaging in vivo. Here, we describe a metastatic cancer cell-targeted protein nanocage. An MMP-2-binding peptide, termed CTT peptide (CTTHWGFTLC), was conjugated [...] Read more.

Matrix metalloproteinase 2 (MMP-2) in metastatic cancer tissue, which is associated with a poor prognosis, is a potential target for tumor imaging in vivo. Here, we describe a metastatic cancer cell-targeted protein nanocage. An MMP-2-binding peptide, termed CTT peptide (CTTHWGFTLC), was conjugated to the surface of a naturally occurring heat shock protein nanocage by genetic modification. The engineered protein nanocages showed a binding affinity for MMP-2 and selective uptake in cancer cells that highly expressed MMP-2 in vitro. In near-infrared fluorescence imaging, the nanocages showed specific and significant accumulation in tumor tissue after intravenous injection in vivo. These protein nanocages conjugated with CTT peptide could be potentially applied to a noninvasive near-infrared fluorescence detection method for imaging gelatinase activity in metastatic tumors in vivo. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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PLGA Biodegradable Nanoparticles Containing Perphenazine or Chlorpromazine Hydrochloride: Effect of Formulation and Release

by Mohammed Halayqa and Urszula Domańska

Int. J. Mol. Sci. 2014, 15(12), 23909-23923; https://doi.org/10.3390/ijms151223909 - 22 Dec 2014

Cited by 68 | Viewed by 10232

Abstract

In our study, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles loaded with perphenazine (PPH) and chlorpromazine hydrochloride (CPZ-HCl) were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol) (PVA) concentration and the power of sonication were [...] Read more.

In our study, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles loaded with perphenazine (PPH) and chlorpromazine hydrochloride (CPZ-HCl) were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol) (PVA) concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM) presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v) in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4) by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Modulation of Induced Cytotoxicity of Doxorubicin by Using Apoferritin and Liposomal Cages

by Jaromir Gumulec, Michaela Fojtu, Martina Raudenska, Marketa Sztalmachova, Anna Skotakova, Jana Vlachova, Sylvie Skalickova, Lukas Nejdl, Pavel Kopel, Lucia Knopfova, Vojtech Adam, Rene Kizek, Marie Stiborova, Petr Babula and Michal Masarik

Int. J. Mol. Sci. 2014, 15(12), 22960-22977; https://doi.org/10.3390/ijms151222960 - 11 Dec 2014

Cited by 33 | Viewed by 9404

Abstract

Doxorubicin is an effective chemotherapeutic drug, however, its toxicity is a significant limitation in therapy. Encapsulation of doxorubicin inside liposomes or ferritin cages decreases cardiotoxicity while maintaining anticancer potency. We synthesized novel apoferritin- and liposome-encapsulated forms of doxorubicin (“Apodox” and “lip-8-dox”) and compared [...] Read more.

Doxorubicin is an effective chemotherapeutic drug, however, its toxicity is a significant limitation in therapy. Encapsulation of doxorubicin inside liposomes or ferritin cages decreases cardiotoxicity while maintaining anticancer potency. We synthesized novel apoferritin- and liposome-encapsulated forms of doxorubicin (“Apodox” and “lip-8-dox”) and compared its toxicity with doxorubicin and Myocet on prostate cell lines. Three different prostatic cell lines PNT1A, 22Rv1, and LNCaP were chosen. The toxicity of the modified doxorubicin forms was compared to conventional doxorubicin using the MTT assay, real-time cell impedance-based cell growth method (RTCA), and flow cytometry. The efficiency of doxorubicin entrapment was 56% in apoferritin cages and 42% in the liposome carrier. The accuracy of the RTCA system was verified by flow-cytometric analysis of cell viability. The doxorubicin half maximal inhibition concentrations (IC₅₀) were determined as 170.5, 234.0, and 169.0 nM for PNT1A, 22Rv1, and LNCaP, respectively by RTCA. Lip8-dox is less toxic on the non-tumor cell line PNT1A compared to doxorubicin, while still maintaining the toxicity to tumorous cell lines similar to doxorubicin or epirubicin (IC₅₀ = 2076.7 nM for PNT1A vs. 935.3 and 729.0 nM for 22Rv1 and LNCaP). Apodox IC₅₀ was determined as follows: 603.1, 1344.2, and 931.2 nM for PNT1A, 22Rv1, and LNCaP. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Polymer Coated CaAl-Layered Double Hydroxide Nanomaterials for Potential Calcium Supplement

by Tae-Hyun Kim, Jeong-A Lee, Soo-Jin Choi and Jae-Min Oh

Int. J. Mol. Sci. 2014, 15(12), 22563-22579; https://doi.org/10.3390/ijms151222563 - 5 Dec 2014

Cited by 24 | Viewed by 7353

Abstract

We have successfully prepared layered double hydroxide (LDH) nanomaterials containing calcium and aluminum ions in the framework (CaAl-LDH). The surface of CaAl-LDH was coated with enteric polymer, Eudragit^®L 100 in order to protect nanomaterials from fast dissolution under gastric condition of [...] Read more.

We have successfully prepared layered double hydroxide (LDH) nanomaterials containing calcium and aluminum ions in the framework (CaAl-LDH). The surface of CaAl-LDH was coated with enteric polymer, Eudragit^®L 100 in order to protect nanomaterials from fast dissolution under gastric condition of pH 1.2. The X-ray diffraction patterns, Fourier transform infrared spectroscopy, scanning electron and transmission electron microscopy revealed that the pristine LDH was well prepared having hydrocalumite structure, and that the polymer effectively coated the surface of LDH without disturbing structure. From thermal analysis, it was determined that only a small amount (less than 1%) of polymer was coated on the LDH surface. Metal dissolution from LDH nanomaterials was significantly reduced upon Eudragit^®L 100 coating at pH 1.2, 6.8 and 7.4, which simulates gastric, enteric and plasma conditions, respectively, and the dissolution effect was the most suppressed at pH 1.2. The LDH nanomaterials did not exhibit any significant cytotoxicity up to 1000 μg/mL and intracellular calcium concentration significantly increased in LDH-treated human intestinal cells. Pharmacokinetic study demonstrated absorption efficiency of Eudragit^®L 100 coated LDH following oral administration to rats. Moreover, the LDH nanomaterials did not cause acute toxic effect in vivo. All the results suggest the great potential of CaAl-LDH nanomaterials as a calcium supplement. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Some Characteristics of Free Cell Population in the Airways of Rats after Intratracheal Instillation of Copper-Containing Nano-Scale Particles

by Larisa I. Privalova, Boris A. Katsnelson, Nadezhda V. Loginova, Vladimir B. Gurvich, Vladimir Y. Shur, Yakov B. Beikin, Marina P. Sutunkova, Ilzira A. Minigalieva, Ekaterina V. Shishkina, Svetlana V. Pichugova, Ludmila G. Tulakina and Svetlana V. Beljayeva

Int. J. Mol. Sci. 2014, 15(11), 21538-21553; https://doi.org/10.3390/ijms151121538 - 24 Nov 2014

Cited by 18 | Viewed by 6270

Abstract

We used stable water suspensions of copper oxide particles with mean diameter 20 nm and of particles containing copper oxide and element copper with mean diameter 340 nm to assess the pulmonary phagocytosis response of rats to a single intratracheal instillation of these [...] Read more.

We used stable water suspensions of copper oxide particles with mean diameter 20 nm and of particles containing copper oxide and element copper with mean diameter 340 nm to assess the pulmonary phagocytosis response of rats to a single intratracheal instillation of these suspensions using optical, transmission electron, and semi-contact atomic force microscopy and biochemical indices measured in the bronchoalveolar lavage fluid. Although both nano and submicron ultrafine particles were adversely bioactive, the former were found to be more toxic for lungs as compared with the latter while evoking more pronounced defense recruitment of alveolar macrophages and especially of neutrophil leukocytes and more active phagocytosis. Based on our results and literature data, we consider both copper solubilization and direct contact with cellular organelles (mainly, mitochondria) of persistent particles internalized by phagocytes as probable mechanisms of their cytotoxicity. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Nickel Nanoparticles Exposure and Reproductive Toxicity in Healthy Adult Rats

by Lu Kong, Meng Tang, Ting Zhang, Dayong Wang, Ke Hu, Weiqi Lu, Chao Wei, Geyu Liang and Yuepu Pu

Int. J. Mol. Sci. 2014, 15(11), 21253-21269; https://doi.org/10.3390/ijms151121253 - 17 Nov 2014

Cited by 156 | Viewed by 14305

Abstract

Nickel is associated with reproductive toxicity. However, the reproductive toxicity of nickel nanoparticles (Ni NPs) is unclear. Our goal was to determine the association between nickel nanoparticle exposure and reproductive toxicity. According to the one-generation reproductive toxicity standard, rats were exposed to nickel [...] Read more.

Nickel is associated with reproductive toxicity. However, the reproductive toxicity of nickel nanoparticles (Ni NPs) is unclear. Our goal was to determine the association between nickel nanoparticle exposure and reproductive toxicity. According to the one-generation reproductive toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including sex hormone levels, sperm motility, histopathology, and reproductive outcome etc. Experimental results showed nickel nanoparticles increased follicle stimulating hormone (FSH) and luteinizing hormone (LH), and lowered etradiol (E₂) serum levels at a dose of 15 and 45 mg/kg in female rats. Ovarian lymphocytosis, vascular dilatation and congestion, inflammatory cell infiltration, and increase in apoptotic cells were found in ovary tissues in exposure groups. For male rats, the weights decreased gradually, the ratio of epididymis weight over body weight increased, the motility of rat sperm changed, and the levels of FSH and testosterone (T) diminished. Pathological results showed the shedding of epithelial cells of raw seminiferous tubule, disordered arrangement of cells in the tube, and the appearance of cell apoptosis and death in the exposure group. At the same time, Ni NPs resulted in a change of the reproductive index and the offspring development of rats. Further research is needed to elucidate exposure to human populations and mechanism of actions. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Spectroscopic Studies of R(+)-α-Lipoic Acid—Cyclodextrin Complexes

by Naoko Ikuta, Akira Tanaka, Ayako Otsubo, Noriko Ogawa, Hiromitsu Yamamoto, Tomoyuki Mizukami, Shoji Arai, Masayuki Okuno, Keiji Terao and Seiichi Matsugo

Int. J. Mol. Sci. 2014, 15(11), 20469-20485; https://doi.org/10.3390/ijms151120469 - 7 Nov 2014

Cited by 31 | Viewed by 8447

Abstract

α-Lipoic acid (ALA) has a chiral center at the C6 position, and exists as two enantiomers, R(+)-ALA (RALA) and S(−)-ALA (SALA). RALA is naturally occurring, and is a cofactor for mitochondrial enzymes, therefore playing a major role in energy metabolism. However, [...] Read more.

α-Lipoic acid (ALA) has a chiral center at the C6 position, and exists as two enantiomers, R(+)-ALA (RALA) and S(−)-ALA (SALA). RALA is naturally occurring, and is a cofactor for mitochondrial enzymes, therefore playing a major role in energy metabolism. However, RALA cannot be used for pharmaceuticals or nutraceuticals because it readily polymerizes via a 1,2-dithiolane ring-opening when exposed to light or heat. So, it is highly desired to find out the method to stabilize RALA. The purpose of this study is to provide the spectroscopic information of stabilized RALA and SALA through complexation with cyclodextrins (CDs), α-CD, β-CD and γ-CD and to examine the physical characteristics of the resultant complexes in the solid state. The RALA-CD structures were elucidated based on the micro fourier transform infrared (FT-IR) and Raman analyses. The FT-IR results showed that the C=O stretching vibration of RALA appeared at 1717 cm⁻¹ and then shifted on formation of the RALA-CD complexes. The Raman spectra showed that the S–S and C–S stretching vibrations for RALA at 511 cm⁻¹ (S–S), 631 cm⁻¹ (C–S) and 675 cm⁻¹ (C–S) drastically weakened and almost disappeared upon complexation with CDs. Several peaks indicative of O–H vibrations also shifted or changed in intensity. These results indicate that RALA and CDs form host-guest complexes by interacting with one another. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Heparin Assisted Photochemical Synthesis of Gold Nanoparticles and Their Performance as SERS Substrates

by Maria Del Pilar Rodríguez-Torres, Luis Armando Díaz-Torres and Sergio Romero-Servin

Int. J. Mol. Sci. 2014, 15(10), 19239-19252; https://doi.org/10.3390/ijms151019239 - 23 Oct 2014

Cited by 37 | Viewed by 9612

Abstract

Reactive and pharmaceutical-grade heparins were used as biologically compatible reducing and stabilizing agents to photochemically synthesize colloidal gold nanoparticles. Aggregates and anisotropic shapes were obtained photochemically under UV black-light lamp irradiation (λ = 366 nm). Heparin-functionalized gold nanoparticles were characterized by Scanning Electron [...] Read more.

Reactive and pharmaceutical-grade heparins were used as biologically compatible reducing and stabilizing agents to photochemically synthesize colloidal gold nanoparticles. Aggregates and anisotropic shapes were obtained photochemically under UV black-light lamp irradiation (λ = 366 nm). Heparin-functionalized gold nanoparticles were characterized by Scanning Electron Microscopy and UV-Vis spectroscopy. The negatively charged colloids were used for the Surface Enhanced Raman Spectroscopy (SERS) analysis of differently charged analytes (dyes). Measurements of pH were taken to inspect how the acidity of the medium affects the colloid-analyte interaction. SERS spectra were taken by mixing the dyes and the colloidal solutions without further functionalization or addition of any aggregating agent. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Discovery and in Vivo Evaluation of Novel RGD-Modified Lipid-Polymer Hybrid Nanoparticles for Targeted Drug Delivery

by Yinbo Zhao, Dayong Lin, Fengbo Wu, Li Guo, Gu He, Liang Ouyang, Xiangrong Song, Wei Huang and Xiang Li

Int. J. Mol. Sci. 2014, 15(10), 17565-17576; https://doi.org/10.3390/ijms151017565 - 29 Sep 2014

Cited by 47 | Viewed by 8141

Abstract

In the current study, the lipid-shell and polymer-core hybrid nanoparticles (lpNPs) modified by Arg–Gly–Asp(RGD) peptide, loaded with curcumin (Cur), were developed by emulsification-solvent volatilization method. The RGD-modified hybrid nanoparticles (RGD–lpNPs) could overcome the poor water solubility of Cur to meet the requirement of [...] Read more.

In the current study, the lipid-shell and polymer-core hybrid nanoparticles (lpNPs) modified by Arg–Gly–Asp(RGD) peptide, loaded with curcumin (Cur), were developed by emulsification-solvent volatilization method. The RGD-modified hybrid nanoparticles (RGD–lpNPs) could overcome the poor water solubility of Cur to meet the requirement of intravenous administration and tumor active targeting. The obtained optimal RGD-lpNPs, composed of PLGA (poly(lactic-co-glycolic acid))–mPEG (methoxyl poly(ethylene- glycol)), RGD–polyethylene glycol (PEG)–cholesterol (Chol) copolymers and lipids, had good entrapment efficiency, submicron size and negatively neutral surface charge. The core-shell structure of RGD–lpNPs was verified by TEM. Cytotoxicity analysis demonstrated that the RGD–lpNPs encapsulated Cur retained potent anti-tumor effects. Flow cytometry analysis revealed the cellular uptake of Cur encapsulated in the RGD–lpNPs was increased for human umbilical vein endothelial cells (HUVEC). Furthermore, Cur loaded RGD–lpNPs were more effective in inhibiting tumor growth in a subcutaneous B16 melanoma tumor model. The results of immunofluorescent and immunohistochemical studies by Cur loaded RGD–lpNPs therapies indicated that more apoptotic cells, fewer microvessels, and fewer proliferation-positive cells were observed. In conclusion, RGD–lpNPs encapsulating Cur were developed with enhanced anti-tumor activity in melanoma, and Cur loaded RGD–lpNPs represent an excellent tumor targeted formulation of Cur which might be an attractive candidate for cancer therapy. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Emodin-Loaded Magnesium Silicate Hollow Nanocarriers for Anti-Angiogenesis Treatment through Inhibiting VEGF

by Hua Ren, Chao Zhu, Zhaohui Li, Wei Yang and E Song

Int. J. Mol. Sci. 2014, 15(9), 16936-16948; https://doi.org/10.3390/ijms150916936 - 23 Sep 2014

Cited by 21 | Viewed by 7539

Abstract

The applications of anti-VEGF (vascular endothelial growth factor) treatment in ophthalmic fields to inhibit angiogenesis have been widely documented in recent years. However, the hydrophobic nature of many agents makes its delivery difficult in practice. Therefore, the aim of the present study was [...] Read more.

The applications of anti-VEGF (vascular endothelial growth factor) treatment in ophthalmic fields to inhibit angiogenesis have been widely documented in recent years. However, the hydrophobic nature of many agents makes its delivery difficult in practice. Therefore, the aim of the present study was to introduce a new kind of hydrophobic drug carrier by employing nanoparticles with a hollow structure inside. Followed by the synthesis and characterization of magnesium silicate hollow spheres, cytotoxicity was evaluated in retina capillary endothelial cells. The loading and releasing capacity were tested by employing emodin, and the effect on VEGF expression was performed at the gene and protein level. Finally, an investigation on angiogenesis was carried on fertilized chicken eggs. The results indicated that the magnesium silicate nanoparticles had low toxicity. Emodin–MgSiO₃ can inhibit the expression of both VEGF gene and protein effectively. Angiogenesis of eggs was also reduced significantly. Based on the above results, we concluded that magnesium silicate hollow spheres were good candidates as drug carriers with enough safety. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Self-Assembled Polymeric Micelles Based on Hyaluronic Acid-g-Poly(d,l-lactide-co-glycolide) Copolymer for Tumor Targeting

by Gyung Mo Son, Hyun Yul Kim, Je Ho Ryu, Chong Woo Chu, Dae Hwan Kang, Su Bum Park and Young-IL Jeong

Int. J. Mol. Sci. 2014, 15(9), 16057-16068; https://doi.org/10.3390/ijms150916057 - 11 Sep 2014

Cited by 56 | Viewed by 8507

Abstract

Graft copolymer composed hyaluronic acid (HA) and poly(d,l-lactide-co-glycolide) (PLGA) (HAgLG) was synthesized for antitumor targeting via CD44 receptor of tumor cells. The carboxylic end of PLGA was conjugated with hexamethylenediamine (HMDA) to have amine end group in the end of chain (PLGA-amine). PLGA-amine [...] Read more.

Graft copolymer composed hyaluronic acid (HA) and poly(d,l-lactide-co-glycolide) (PLGA) (HAgLG) was synthesized for antitumor targeting via CD44 receptor of tumor cells. The carboxylic end of PLGA was conjugated with hexamethylenediamine (HMDA) to have amine end group in the end of chain (PLGA-amine). PLGA-amine was coupled with carboxylic acid of HA. Self-assembled polymeric micelles of HAgLG have spherical morphologies and their sizes were around 50–200 nm. Doxorubicin (DOX)-incorporated polymeric micelles were prepared by dialysis procedure. DOX was released over 4 days and its release rate was accelerated by the tumoric enzyme hyaluronidase. To assess targetability of polymeric micelles, CD44-positive HepG2 cells were employed treated with fluorescein isothiocyanate (FITC)-labeled polymeric micelles. HepG2 cells strongly expressed green fluorescence at the cell membrane and cytosol. However, internalization of polymeric micelles were significantly decreased when free HA was pretreated to block the CD44 receptor. Furthermore, the CD44-specific anticancer activity of HAgLG polymeric micelles was confirmed using CD44-negative CT26 cells and CD44-positive HepG2 cells. These results indicated that polymeric micelles of HaLG polymeric micelles have targetability against CD44 receptor of tumor cells. We suggest HAgLG polymeric micelles as a promising candidate for specific drug targeting. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Adsorption of Bisphenol A to a Carbon Nanotube Reduced Its Endocrine Disrupting Effect in Mice Male Offspring

by Wenwei Wang, Cuijuan Jiang, Ledong Zhu, Nana Liang, Xuejiao Liu, Jianbo Jia, Chengke Zhang, Shumei Zhai and Bin Zhang

Int. J. Mol. Sci. 2014, 15(9), 15981-15993; https://doi.org/10.3390/ijms150915981 - 10 Sep 2014

Cited by 21 | Viewed by 8064

Abstract

Soluble carbon nanotubes (CNTs) have shown promise as materials for adsorption of environmental contaminants such as Bisphenol A (BPA), due to the high adsorption capacity and strong desorption hysteresis of BPA on CNTs. The adsorption of BPA to CNTs may change the properties [...] Read more.

Soluble carbon nanotubes (CNTs) have shown promise as materials for adsorption of environmental contaminants such as Bisphenol A (BPA), due to the high adsorption capacity and strong desorption hysteresis of BPA on CNTs. The adsorption of BPA to CNTs may change the properties of both BPA and CNTs, and induce different toxicity to human and living systems from that of BPA and CNTs alone. Herein, we report that oral exposure of BPA/MWCNT–COOH (carboxylated multi-walled carbon nantubes) adduct to mice during gestation and lactation period decreased the male offspring reproductive toxicity compared with those induced by BPA alone. The adduct decreased malondialdehyde (MDA) level in testis and follicle-stimulating hormone (FSH) in serum, but increased the level of serum testosterone in male offspring in comparison to BPA alone. Our investigations broadened the knowledge of nanotoxicity and provided important information on the safe application of CNTs. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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In Vivo Immunotoxicity of SiO2@(Y0.5Gd0.45Eu0.05)2O3 as Dual-Modality Nanoprobes

by Xiumei Tian, Ermao Li, Fanwen Yang, Ye Peng, Jixiang Zhu, Fupo He and Xiaoming Chen

Int. J. Mol. Sci. 2014, 15(8), 13649-13662; https://doi.org/10.3390/ijms150813649 - 7 Aug 2014

Cited by 1 | Viewed by 6380

Abstract

We have successfully synthesized SiO₂@(Y_0.₅Gd_0.45Eu_0.05)₂O₃ nanocomposites as a potential dual-modality nanoprobe for molecular imaging in vitro. However, their immunotoxicity assessment in vivo remains unknown. In this article, the in vitro [...] Read more.

We have successfully synthesized SiO₂@(Y_0.₅Gd_0.45Eu_0.05)₂O₃ nanocomposites as a potential dual-modality nanoprobe for molecular imaging in vitro. However, their immunotoxicity assessment in vivo remains unknown. In this article, the in vitro biocompatibility of our dual-modality nanoprobes was assayed in terms of cell viability and apoptosis. In vivo immunotoxicity was investigated by monitoring the generation of reactive oxygen species (ROS), cluster of differentiation (CD) markers and cytokines in Balb/c mice. The data show that the in vitro biocompatibility was satisfactory. In addition, the immunotoxicity data revealed there are no significant changes in the expression levels of CD11b and CD71 between the nanoprobe group and the Gd in a diethylenetriaminepentaacetic acid (DTPA) chelator (Gd-DTPA) group 24 h after injection in Balb/c mice (p > 0.05). Importantly, there are significant differences in the expression levels of CD206 and CD25 as well as the secretion of IL-4 and the generation of ROS 24 h after injection (p < 0.05). Transmission electron microscopy (TEM) images showed that few nanoprobes were localized in the phagosomes of liver and lung. In conclusion, the toxic effects of our nanoprobes may mainly result from the aggregation of particles in phagosomes. This accumulation may damage the microstructure of the cells and generate oxidative stress reactions that further stimulate the immune response. Therefore, it is important to evaluate the in vivo immunotoxicity of these rare earth-based biomaterials at the molecular level before molecular imaging in vivo. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Subchronic Toxicity of Copper Oxide Nanoparticles and Its Attenuation with the Help of a Combination of Bioprotectors

by Larisa I. Privalova, Boris A. Katsnelson, Nadezhda V. Loginova, Vladimir B. Gurvich, Vladimir Y. Shur, Irene E. Valamina, Oleg H. Makeyev, Marina P. Sutunkova, Ilzira A. Minigalieva, Ekaterina P. Kireyeva, Vadim O. Rusakov, Anastasia E. Tyurnina, Roman V. Kozin, Ekaterina Y. Meshtcheryakova, Artem V. Korotkov, Eugene A. Shuman, Anastasia E. Zvereva and Svetlana V. Kostykova

Int. J. Mol. Sci. 2014, 15(7), 12379-12406; https://doi.org/10.3390/ijms150712379 - 14 Jul 2014

Cited by 61 | Viewed by 9930

Abstract

In the copper metallurgy workplace air is polluted with condensation aerosols, which a significant fraction of is presented by copper oxide particles <100 nm. In the scientific literature, there is a lack of their in vivo toxicity characterization and virtually no attempts of [...] Read more.

In the copper metallurgy workplace air is polluted with condensation aerosols, which a significant fraction of is presented by copper oxide particles <100 nm. In the scientific literature, there is a lack of their in vivo toxicity characterization and virtually no attempts of enhancing organism’s resistance to their impact. A stable suspension of copper oxide particles with mean (±SD) diameter 20 ± 10 nm was prepared by laser ablation of pure copper in water. It was being injected intraperitoneally to rats at a dose of 10 mg/kg (0.5 mg per mL of deionized water) three times a week up to 19 injections. In parallel, another group of rats was so injected with the same suspension against the background of oral administration of a “bio-protective complex” (BPC) comprising pectin, a multivitamin-multimineral preparation, some amino acids and fish oil rich in ω-3 PUFA. After the termination of injections, many functional and biochemical indices for the organism’s status, as well as pathological changes of liver, spleen, kidneys, and brain microscopic structure were evaluated for signs of toxicity. In the same organs we have measured accumulation of copper while their cells were used for performing the Random Amplification of Polymorphic DNA (RAPD) test for DNA fragmentation. The same features were assessed in control rats infected intraperitoneally with water with or without administration of the BPC. The copper oxide nanoparticles proved adversely bio-active in all respects considered in this study, their active in vivo solubilization in biological fluids playing presumably an important role in both toxicokinetics and toxicodynamics. The BPC proposed and tested by us attenuated systemic and target organs toxicity, as well as genotoxicity of this substance. Judging by experimental data obtained in this investigation, occupational exposures to nano-scale copper oxide particles can present a significant health risk while the further search for its management with the help of innocuous bioprotectors seems to be justified. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Open AccessArticle

Effects of Silica and Titanium Oxide Particles on a Human Neural Stem Cell Line: Morphology, Mitochondrial Activity, and Gene Expression of Differentiation Markers

by Kouki Fujioka, Sanshiro Hanada, Yuriko Inoue, Keisuke Sato, Kenji Hirakuri, Kouichi Shiraishi, Fumihide Kanaya, Keiichi Ikeda, Ritsuko Usui, Kenji Yamamoto, Seung U. Kim and Yoshinobu Manome

Int. J. Mol. Sci. 2014, 15(7), 11742-11759; https://doi.org/10.3390/ijms150711742 - 2 Jul 2014

Cited by 30 | Viewed by 8480

Abstract

Several in vivo studies suggest that nanoparticles (smaller than 100 nm) have the ability to reach the brain tissue. Moreover, some nanoparticles can penetrate into the brains of murine fetuses through the placenta by intravenous administration to pregnant mice. However, it is not [...] Read more.

Several in vivo studies suggest that nanoparticles (smaller than 100 nm) have the ability to reach the brain tissue. Moreover, some nanoparticles can penetrate into the brains of murine fetuses through the placenta by intravenous administration to pregnant mice. However, it is not clear whether the penetrated nanoparticles affect neurogenesis or brain function. To evaluate its effects on neural stem cells, we assayed a human neural stem cell (hNSCs) line exposed in vitro to three types of silica particles (30 nm, 70 nm, and <44 µm) and two types of titanium oxide particles (80 nm and < 44 µm). Our results show that hNSCs aggregated and exhibited abnormal morphology when exposed to the particles at concentrations = 0.1 mg/mL for 7 days. Moreover, all the particles affected the gene expression of Nestin (stem cell marker) and neurofilament heavy polypeptide (NF-H, neuron marker) at 0.1 mg/mL. In contrast, only 30-nm silica particles at 1.0 mg/mL significantly reduced mitochondrial activity. Notably, 30-nm silica particles exhibited acute membrane permeability at concentrations =62.5 µg/mL in 24 h. Although these concentrations are higher than the expected concentrations of nanoparticles in the brain from in vivo experiments in a short period, these thresholds may indicate the potential toxicity of accumulated particles for long-term usage or continuous exposure. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Open AccessArticle

Efficient Delivery of Plasmid DNA Using Cholesterol-Based Cationic Lipids Containing Polyamines and Ether Linkages

by Bieong-Kil Kim, Young-Bae Seu, Yun-Ui Bae, Tae-Won Kwak, Hyungu Kang, Ik-Jae Moon, Guen-Bae Hwang, So-Young Park and Kyung-Oh Doh

Int. J. Mol. Sci. 2014, 15(5), 7293-7312; https://doi.org/10.3390/ijms15057293 - 28 Apr 2014

Cited by 14 | Viewed by 10739

Abstract

Cationic liposomes are broadly used as non-viral vectors to deliver genetic materials that can be used to treat various diseases including cancer. To circumvent problems associated with cationic liposome-mediated delivery systems such as low transfection efficiency and serum-induced inhibition, cholesterol-based cationic lipids have [...] Read more.

Cationic liposomes are broadly used as non-viral vectors to deliver genetic materials that can be used to treat various diseases including cancer. To circumvent problems associated with cationic liposome-mediated delivery systems such as low transfection efficiency and serum-induced inhibition, cholesterol-based cationic lipids have been synthesized that resist the effects of serum. The introduction of an ether-type linkage and extension of the aminopropyl head group on the cholesterol backbone increased the transfection efficiency and DNA binding affinity compared to a carbamoyl-type linkage and a mono aminopropyl head group, respectively. Under optimal conditions, each liposome formulation showed higher transfection efficiency in AGS and Huh-7 cells than commercially available cationic liposomes, particularly in the presence of serum. The following molecular structures were found to have a positive effect on transfection properties: (i) extended aminopropyl head groups for a strong binding affinity to plasmid DNA; (ii) an ether linkage that favors electrostatic binding to plasmid DNA; and (iii) a cholesterol backbone for serum resistance. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Preparation and Characterization of Gelatin Nanofibers Containing Silver Nanoparticles

by Lim Jeong and Won Ho Park

Int. J. Mol. Sci. 2014, 15(4), 6857-6879; https://doi.org/10.3390/ijms15046857 - 22 Apr 2014

Cited by 78 | Viewed by 11882

Abstract

Ag nanoparticles (NPs) were synthesized in formic acid aqueous solutions through chemical reduction. Formic acid was used for a reducing agent of Ag precursor and solvent of gelatin. Silver acetate, silver tetrafluoroborate, silver nitrate, and silver phosphate were used as Ag precursors. Ag [...] Read more.

Ag nanoparticles (NPs) were synthesized in formic acid aqueous solutions through chemical reduction. Formic acid was used for a reducing agent of Ag precursor and solvent of gelatin. Silver acetate, silver tetrafluoroborate, silver nitrate, and silver phosphate were used as Ag precursors. Ag⁺ ions were reduced into Ag NPs by formic acid. The formation of Ag NPs was characterized by a UV-Vis spectrophotometer. Ag NPs were quickly generated within a few minutes in silver nitrate (AgNO₃)/formic acid solution. As the water content of formic acid aqueous solution increased, more Ag NPs were generated, at a higher rate and with greater size. When gelatin was added to the AgNO₃/formic acid solution, the Ag NPs were stabilized, resulting in smaller particles. Moreover, gelatin limits further aggregation of Ag NPs, which were effectively dispersed in solution. The amount of Ag NPs formed increased with increasing concentration of AgNO₃ and aging time. Gelatin nanofibers containing Ag NPs were fabricated by electrospinning. The average diameters of gelatin nanofibers were 166.52 ± 32.72 nm, but these decreased with the addition of AgNO₃. The average diameters of the Ag NPs in gelatin nanofibers ranged between 13 and 25 nm, which was confirmed by transmission electron microscopy (TEM). Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Development of Lipid-Shell and Polymer Core Nanoparticles with Water-Soluble Salidroside for Anti-Cancer Therapy

by Dai-Long Fang, Yan Chen, Bei Xu, Ke Ren, Zhi-Yao He, Li-Li He, Yi Lei, Chun-Mei Fan and Xiang-Rong Song

Int. J. Mol. Sci. 2014, 15(3), 3373-3388; https://doi.org/10.3390/ijms15033373 - 25 Feb 2014

Cited by 72 | Viewed by 10511

Abstract

Salidroside (Sal) is a potent antitumor drug with high water-solubility. The clinic application of Sal in cancer therapy has been significantly restricted by poor oral absorption and low tumor cell uptake. To solve this problem, lipid-shell and polymer-core nanoparticles (Sal-LPNPs) loaded with Sal [...] Read more.

Salidroside (Sal) is a potent antitumor drug with high water-solubility. The clinic application of Sal in cancer therapy has been significantly restricted by poor oral absorption and low tumor cell uptake. To solve this problem, lipid-shell and polymer-core nanoparticles (Sal-LPNPs) loaded with Sal were developed by a double emulsification method. The processing parameters including the polymer types, organic phase, PVA types and amount were systemically investigated. The obtained optimal Sal-LPNPs, composed of PLGA-PEG-PLGA triblock copolymers and lipids, had high entrapment efficiency (65%), submicron size (150 nm) and negatively charged surface (−23 mV). DSC analysis demonstrated the successful encapsulation of Sal into LPNPs. The core-shell structure of Sal-LPNPs was verified by TEM. Sal released slowly from the LPNPs without apparent burst release. MTT assay revealed that 4T1 and PANC-1 cancer cell lines were sensitive to Sal treatment. Sal-LPNPs had significantly higher antitumor activities than free Sal in 4T1 and PANC-1 cells. The data indicate that LPNPs are a promising Sal vehicle for anti-cancer therapy and worthy of further investigation. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Dual Agent Loaded PLGA Nanoparticles Enhanced Antitumor Activity in a Multidrug-Resistant Breast Tumor Xenograft Model

by Yan Chen, Xue-Lian Zheng, Dai-Long Fang, Yang Yang, Jin-Kun Zhang, Hui-Li Li, Bei Xu, Yi Lei, Ke Ren and Xiang-Rong Song

Int. J. Mol. Sci. 2014, 15(2), 2761-2772; https://doi.org/10.3390/ijms15022761 - 18 Feb 2014

Cited by 37 | Viewed by 7957 | Correction

Abstract

Multidrug-resistant breast cancers have limited and ineffective clinical treatment options. This study aimed to develop PLGA nanoparticles containing a synergistic combination of vincristine and verapamil to achieve less toxicity and enhanced efficacy on multidrug-resistant breast cancers. The 1:250 molar ratio of VCR/VRP showed [...] Read more.

Multidrug-resistant breast cancers have limited and ineffective clinical treatment options. This study aimed to develop PLGA nanoparticles containing a synergistic combination of vincristine and verapamil to achieve less toxicity and enhanced efficacy on multidrug-resistant breast cancers. The 1:250 molar ratio of VCR/VRP showed strong synergism with the reversal index of approximately 130 in the multidrug-resistant MCF-7/ADR cells compared to drug-sensitive MCF-7 cells. The lyophilized nanoparticles could get dispersed quickly with the similar size distribution, zeta potential and encapsulation efficiency to the pre-lyophilized nanoparticles suspension, and maintain the synergistic in vitro release ratio of drugs. The co-encapsulated nanoparticle formulation had lower toxicity than free vincristine/verapamil combinations according to the acute-toxicity test. Furthermore, the most effective tumor growth inhibition in the MCF-7/ADR human breast tumor xenograft was observed in the co-delivery nanoparticle formulation group in comparison with saline control, free vincristine, free vincristine/verapamil combinations and single-drug nanoparticle combinations. All the data demonstrated that PLGANPs simultaneously loaded with chemotherapeutic drug and chemosensitizer might be one of the most potential formulations in the treatment of multidrug-resistant breast cancer in clinic. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Preparation and Characterization of Tripterygium wilfordii Multi-Glycoside Nanoparticle Using Supercritical Anti-Solvent Process

by Fengli Chen, Tong Li, Shuangyang Li, Kexin Hou, Zaizhi Liu, Lili Li, Guoqiang Cui, Yuangang Zu and Lei Yang

Int. J. Mol. Sci. 2014, 15(2), 2695-2711; https://doi.org/10.3390/ijms15022695 - 17 Feb 2014

Cited by 10 | Viewed by 7969

Abstract

The aim of this study was to prepare nanosized Tripterygium wilfordii multi-glycoside (GTW) powders by the supercritical antisolvent precipitation process (SAS), and to evaluate the anti-inflammatory effects. Ethanol was used as solvent and carbon dioxide was used as an antisolvent. The effects of [...] Read more.

The aim of this study was to prepare nanosized Tripterygium wilfordii multi-glycoside (GTW) powders by the supercritical antisolvent precipitation process (SAS), and to evaluate the anti-inflammatory effects. Ethanol was used as solvent and carbon dioxide was used as an antisolvent. The effects of process parameters such as precipitation pressure (15–35 MPa), precipitation temperature (45–65 °C), drug solution flow rates (3–7 mL/min) and drug concentrations (10–30 mg/mL) were investigated. The nanospheres obtained with mean diameters ranged from 77.5 to 131.8 nm. The processed and unprocessed GTW were characterized by scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy and thermal gravimetric analysis. The present study was designed to investigate the beneficial effect of the GTW nanoparticles on adjuvant-induced arthritis in albino rats. The processed and unprocessed GTW were tested against Freund’s complete adjuvant-induced arthritis in rats. Blood samples were collected for the estimation of interleukins (IL-1α, IL-1β) and tumor necrosis factor-α (TNF-α). It was concluded that physicochemical properties and anti-inflammatory activity of GTW nanoparticles could be improved by physical modification, such as particle size reduction using supercritical antisolvent (SAS) process. Further, SAS process was a powerful methodology for improving the physicochemical properties and anti-inflammatory activity of GTW. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Comparability of in Vitro Tests for Bioactive Nanoparticles: A Common Assay to Detect Reactive Oxygen Species as an Example

by Matthias Roesslein, Cordula Hirsch, Jean-Pierre Kaiser, Harald F. Krug and Peter Wick

Int. J. Mol. Sci. 2013, 14(12), 24320-24337; https://doi.org/10.3390/ijms141224320 - 13 Dec 2013

Cited by 78 | Viewed by 9544

Abstract

The release of reactive oxygen species (ROS) during the electron transport of mitochondrial aerobic respiration is the major source of ROS. However, contact between cells and nanoparticles (NPs) can also induce release of ROS, leading to an imbalance towards the pro-oxidative state. At [...] Read more.

The release of reactive oxygen species (ROS) during the electron transport of mitochondrial aerobic respiration is the major source of ROS. However, contact between cells and nanoparticles (NPs) can also induce release of ROS, leading to an imbalance towards the pro-oxidative state. At low levels of ROS production, cells initiate a protective response to guarantee their survival, but an excess of ROS can damage cellular compounds such as membranes and various organelles, or directly cause genotoxicity. Thus an elevated level of ROS is an important indicator of cellular stress and an accurate recording of this parameter would be very informative. ROS can be measured by various assays, but all known assays measuring and quantifying ROS possess certain weaknesses. The problems and challenges of quantitatively detecting ROS in vitro using the 2',7'-dichlorodihydrofluorescein (DCF) assay is discussed as an example. In addition, we debate the difficulties in finding a suitable and stable chemical reaction control for the DCF assay (or other ROS-detecting assays). As a conclusion, we believe that using 3-morpholinosydnonimine hydrochloride (Sin-1) as a ROS inducer in the DCF assay is feasible only qualitatively. However, a quantitative measurement of the absolute amount of ROS produced and a quantitative comparison between experiments is (at the moment) impossible. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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The Preparation of Capsaicin-Chitosan Microspheres (CCMS) Enteric Coated Tablets

by Jian Chen, Gui-Dong Huang, Si-Rong Tan, Jiao Guo and Zheng-Quan Su

Int. J. Mol. Sci. 2013, 14(12), 24305-24319; https://doi.org/10.3390/ijms141224305 - 13 Dec 2013

Cited by 19 | Viewed by 9399

Abstract

This study aimed to research the preparation and content determination of capsaicin-chitosan microspheres (CCMS) enteric coated tablets. The core tablets were prepared with the method of wet granulation. Nine formulae were designed to determine the optimal formula of the core tablet. Eudragit L100 [...] Read more.

This study aimed to research the preparation and content determination of capsaicin-chitosan microspheres (CCMS) enteric coated tablets. The core tablets were prepared with the method of wet granulation. Nine formulae were designed to determine the optimal formula of the core tablet. Eudragit L100 was used to prepare the CCMS enteric-coated tablets. The effect of enteric coated formulation variables such as content of talc (10%, 25% and 40%), plasticisers (TEC and DBS), dosage of plasticiser (10%, 20% and 30%) and coating weight (2%, 3% and 5%) were evaluated for drug release characteristics. The in vitro release was studied using 0.1 N HCl and pH 6.8 phosphate buffer. Enteric coated tablets without ruptures or swelling behaviour over 2 h in 0.1 N HCl indicated that these tablets showed acid resistance. The accumulated release rate in phosphate buffer (pH 6.8) revealed that the prepared tablets were able to sustain drug release into the intestine and a first-order release was obtained for capsaicin. This research is the first report of the preparation and content determination of CCMS enteric coated tablets. The sustained release behavior of enteric coated formulations in pH 6.8 phosphate buffer demonstrated that it would be a potential drug delivery platform for sustained delivery of gastric irritant drugs. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Optimized Production of Biodiesel from Waste Cooking Oil by Lipase Immobilized on Magnetic Nanoparticles

by Chi-Yang Yu, Liang-Yu Huang, I-Ching Kuan and Shiow-Ling Lee

Int. J. Mol. Sci. 2013, 14(12), 24074-24086; https://doi.org/10.3390/ijms141224074 - 11 Dec 2013

Cited by 68 | Viewed by 8251

Abstract

Biodiesel, a non-toxic and biodegradable fuel, has recently become a major source of renewable alternative fuels. Utilization of lipase as a biocatalyst to produce biodiesel has advantages over common alkaline catalysts such as mild reaction conditions, easy product separation, and use of waste [...] Read more.

Biodiesel, a non-toxic and biodegradable fuel, has recently become a major source of renewable alternative fuels. Utilization of lipase as a biocatalyst to produce biodiesel has advantages over common alkaline catalysts such as mild reaction conditions, easy product separation, and use of waste cooking oil as raw material. In this study, Pseudomonas cepacia lipase immobilized onto magnetic nanoparticles (MNP) was used for biodiesel production from waste cooking oil. The optimal dosage of lipase-bound MNP was 40% (w/w of oil) and there was little difference between stepwise addition of methanol at 12 h- and 24 h-intervals. Reaction temperature, substrate molar ratio (methanol/oil), and water content (w/w of oil) were optimized using response surface methodology (RSM). The optimal reaction conditions were 44.2 °C, substrate molar ratio of 5.2, and water content of 12.5%. The predicted and experimental molar conversions of fatty acid methyl esters (FAME) were 80% and 79%, respectively. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Self/Co-Assembling Peptide, EAR8-II, as a Potential Carrier for a Hydrophobic Anticancer Drug Pirarubicin (THP)—Characterization and in-Vitro Delivery

by Parisa Sadatmousavi and P. Chen

Int. J. Mol. Sci. 2013, 14(12), 23315-23329; https://doi.org/10.3390/ijms141223315 - 26 Nov 2013

Cited by 11 | Viewed by 6428

Abstract

A short ionic-complementary peptide, EAR8-II, was employed to encapsulate the hydrophobic anticancer drug pirarubicin (THP). EAR8-II was designed to inherit advantages from two previously introduced peptides, AAP8 and EAK16-II, in their self/co-assembly. This peptide is short, simple, and inexpensive to synthesize, while possessing [...] Read more.

A short ionic-complementary peptide, EAR8-II, was employed to encapsulate the hydrophobic anticancer drug pirarubicin (THP). EAR8-II was designed to inherit advantages from two previously introduced peptides, AAP8 and EAK16-II, in their self/co-assembly. This peptide is short, simple, and inexpensive to synthesize, while possessing a low critical assembly concentration (CAC). The choice of alanine (A) residues in the peptide sequence provides moderate hydrophobic interactions, causing a minimal degree of aggregation, compared with other more hydrophobic residues. EAR8-II is an ionic-complementary peptide, similar to EAK16-II, can self/co-assemble with hydrophobic compounds such as THP, and forms a stable fibular nanostructure in aqueous solution. Physiochemical properties and cellular activities of the EAR8-II and THP complexes were evaluated and show dependency on the peptide-to-drug ratio. The complex at the peptide-to-drug mass ratio of 5:1 provides a stable solution, uniform nanostructure, and highly effective anticancer activity against various cancer cell lines. This work forms the basis for detailed studies on EAR8-II and THP formulations in vitro and in vivo, for future development of peptide-based delivery systems for hydrophobic anticancer drugs. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2013)

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Size-Dependent Cytotoxicity of Nanocarbon Blacks

by Huating Kong, Yu Zhang, Yongjun Li, Zhifen Cui, Kai Xia, Yanhong Sun, Qunfen Zhao and Ying Zhu

Int. J. Mol. Sci. 2013, 14(11), 22529-22543; https://doi.org/10.3390/ijms141122529 - 14 Nov 2013

Cited by 19 | Viewed by 6659

Abstract

In this study, we investigated the toxic effects of nanocarbon blacks (NCBs) with different sizes to mouse macrophage RAW264.7 cells. MTT and fluorescence-based LIVE assays demonstrated that NCBs uptake caused a size and dose-dependent growth inhibition to the cells. Optical microscopy observations and [...] Read more.

In this study, we investigated the toxic effects of nanocarbon blacks (NCBs) with different sizes to mouse macrophage RAW264.7 cells. MTT and fluorescence-based LIVE assays demonstrated that NCBs uptake caused a size and dose-dependent growth inhibition to the cells. Optical microscopy observations and ^99mTc radionuclide labeling techniques were used to investigate the cellular uptake of NCBs with different sizes qualitatively and quantitatively, respectively. Results showed that the cellular uptake amounts of NCBs increased with their increasing size. Large quantities of internal NCBs induced oxidative stress and nuclear damage in cells; these effects may be the critical factors involved in the cytotoxicity of NCBs. The implications associated with these findings are discussed. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2013)

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The Anti-Fasciolasis Properties of Silver Nanoparticles Produced by Trichoderma harzianum and Their Improvement of the Anti-Fasciolasis Drug Triclabendazole

by Youssuf A. Gherbawy, Ismail M. Shalaby, Mahmoud Syed Abd El-sadek, Hesham M. Elhariry and AbdelElah A. Banaja

Int. J. Mol. Sci. 2013, 14(11), 21887-21898; https://doi.org/10.3390/ijms141121887 - 5 Nov 2013

Cited by 45 | Viewed by 8781

Abstract

Recently, new strains of Fasciola demonstrated drug resistance, which increased the need for new drugs or improvement of the present drugs. Nanotechnology is expected to open some new opportunities to fight and prevent diseases using an atomic scale tailoring of materials. The ability [...] Read more.

Recently, new strains of Fasciola demonstrated drug resistance, which increased the need for new drugs or improvement of the present drugs. Nanotechnology is expected to open some new opportunities to fight and prevent diseases using an atomic scale tailoring of materials. The ability to uncover the structure and function of biosystems at the nanoscale, stimulates research leading to improvement in biology, biotechnology, medicine and healthcare. The size of nanomaterials is similar to that of most biological molecules and structures; therefore, nanomaterials can be useful for both in vivo and in vitro biomedical research and applications. Therefore, this work aimed to isolate fungal strains from Taif soil samples, which have the ability to synthesize silver nanoparticles. The fungus Trichoderma harzianum, when challenged with silver nitrate solution, accumulated silver nanoparticles (AgNBs) on the surface of its cell wall in 72 h. These nanoparticles, dislodged by ultrasonication, showed an absorption peak at 420 nm in a UV-visible spectrum, corresponding to the plasmon resonance of silver nanoparticles. The transmission electron micrographs of dislodged nanoparticles in aqueous solution showed the production of reasonably monodisperse silver nanoparticles (average particle size: 4.66 nm) by the fungus. The percentage of non hatching eggs treated with the Triclabendazole drug was 69.67%, while this percentage increased to 89.67% in combination with drug and AgNPs. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2013)

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Fast Disintegrating Quercetin-Loaded Drug Delivery Systems Fabricated Using Coaxial Electrospinning

by Xiao-Yan Li, Yan-Chun Li, Deng-Guang Yu, Yao-Zu Liao and Xia Wang

Int. J. Mol. Sci. 2013, 14(11), 21647-21659; https://doi.org/10.3390/ijms141121647 - 31 Oct 2013

Cited by 63 | Viewed by 11149

Abstract

The objective of this study is to develop a structural nanocomposite of multiple components in the form of core-sheath nanofibres using coaxial electrospinning for the fast dissolving of a poorly water-soluble drug quercetin. Under the selected conditions, core-sheath nanofibres with quercetin and sodium [...] Read more.

The objective of this study is to develop a structural nanocomposite of multiple components in the form of core-sheath nanofibres using coaxial electrospinning for the fast dissolving of a poorly water-soluble drug quercetin. Under the selected conditions, core-sheath nanofibres with quercetin and sodium dodecyl sulphate (SDS) distributed in the core and sheath part of nanofibres, respectively, were successfully generated, and the drug content in the nanofibres was able to be controlled simply through manipulating the core fluid flow rates. Field emission scanning electron microscope (FESEM) images demonstrated that the nanofibres prepared from the single sheath fluid and double core/sheath fluids (with core-to-sheath flow rate ratios of 0.4 and 0.7) have linear morphology with a uniform structure and smooth surface. The TEM images clearly demonstrated the core-sheath structures of the produced nanocomposites. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) results verified that quercetin and SDS were well distributed in the polyvinylpyrrolidone (PVP) matrix in an amorphous state, due to the favourite second-order interactions. In vitro dissolution studies showed that the core-sheath composite nanofibre mats could disintegrate rapidly to release quercetin within 1 min. The study reported here provides an example of the systematic design, preparation, characterization and application of a new type of structural nanocomposite as a fast-disintegrating drug delivery system. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2013)

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Preparation and Characterization of Nanoliposomes Entrapping Medium-Chain Fatty Acids and Vitamin C by Lyophilization

by Shuibing Yang, Chengmei Liu, Wei Liu, Haixia Yu, Huijuan Zheng, Wei Zhou and Yaqin Hu

Int. J. Mol. Sci. 2013, 14(10), 19763-19773; https://doi.org/10.3390/ijms141019763 - 30 Sep 2013

Cited by 61 | Viewed by 8284

Abstract

The complex nanoliposomes encapsulating both a hydrophilic drug vitamin C (vit C) and hydrophobic drug medium-chain fatty acids (MCFAs) was prepared by combining double emulsion method with dynamic high pressure microfluidization. The complex nanoliposomes was further freeze-dried under −86 °C for 48 h [...] Read more.

The complex nanoliposomes encapsulating both a hydrophilic drug vitamin C (vit C) and hydrophobic drug medium-chain fatty acids (MCFAs) was prepared by combining double emulsion method with dynamic high pressure microfluidization. The complex nanoliposomes was further freeze-dried under −86 °C for 48 h with sucrose at the sucrose/lipids ratio of 2:1(w/w) in order to enhance its stability. The freeze-dried complex nanoliposomes under the suitable conditions exhibited high entrapment efficiency of MCFAs (44.26 ± 3.34)%, relatively high entrapment efficiency of vit C (62.25 ± 3.43)%, low average size diameter (110.4 ± 7.28) nm and good storage stability at 4 °C for 60 days with slight changes in mean particle diameter and drug entrapment efficiencies. The results of transmission electron microscopy of freeze-dried complex nanoliposomes also showed that the freeze-dried samples with sucrose were stable without great increase in their particle sizes and without destroying their spherical shape. The results indicated that sucrose presented well protection effects in MCFAs-vit C complex nanoliposomes, suggesting the possibility of further usage in commercial liposomes. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2013)

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Galactosylated Chitosan Oligosaccharide Nanoparticles for Hepatocellular Carcinoma Cell-Targeted Delivery of Adenosine Triphosphate

by Xiu Liang Zhu, Yong Zhong Du, Ri Sheng Yu, Ping Liu, Dan Shi, Ying Chen, Ying Wang and Fang Fang Huang

Int. J. Mol. Sci. 2013, 14(8), 15755-15766; https://doi.org/10.3390/ijms140815755 - 29 Jul 2013

Cited by 47 | Viewed by 9762

Abstract

Nanoparticles composed of galactosylated chitosan oligosaccharide (Gal-CSO) and adenosine triphosphate (ATP) were prepared for hepatocellular carcinoma cell-specific uptake, and the characteristics of Gal-CSO/ATP nanoparticles were evaluated. CSO/ATP nanoparticles were prepared as a control. The average diameter and zeta potential of Gal-CSO/ATP nanoparticles were [...] Read more.

Nanoparticles composed of galactosylated chitosan oligosaccharide (Gal-CSO) and adenosine triphosphate (ATP) were prepared for hepatocellular carcinoma cell-specific uptake, and the characteristics of Gal-CSO/ATP nanoparticles were evaluated. CSO/ATP nanoparticles were prepared as a control. The average diameter and zeta potential of Gal-CSO/ATP nanoparticles were 51.03 ± 3.26 nm and 30.50 ± 1.25 mV, respectively, suggesting suitable properties for a drug delivery system. Subsequently, the cytotoxicity of Gal-CSO/ATP nanoparticles were examined by the methyl tetrazolium (MTT) assay, and the half maximal inhibitory concentration (IC₅₀) values were calculated with HepG2 (human hepatocellular carcinoma cell line) cells. The results showed that the cytotoxic effect of nanoparticles on HepG2 cells was low. In the meantime, it was also found that the Gal-CSO/ATP nanoparticles could be uptaken by HepG2 cells, due to expression of the asialoglycoprotein receptor (ASGP-R) on their surfaces. The presented results indicate that the Gal-CSO nanoparticles might be very attractive to be used as an intracellular drug delivery carrier for hepatocellular carcinoma cell targeting, thus warranting further in vivo or clinical investigations. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2013)

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Synergistic Effects of Nano-Sized Titanium Dioxide and Zinc on the Photosynthetic Capacity and Survival of Anabaena sp.

by Yulin Tang, Shuyan Li, Junlian Qiao, Hongtao Wang and Lei Li

Int. J. Mol. Sci. 2013, 14(7), 14395-14407; https://doi.org/10.3390/ijms140714395 - 11 Jul 2013

Cited by 53 | Viewed by 7924

Abstract

Anabaena sp. was used to examine the toxicity of exposure to a nano-TiO₂ suspension, Zn²⁺ solution, and mixtures of nano-TiO₂ and Zn²⁺ suspensions. Typical chlorophyll fluorescence parameters, including effective quantum yield, photosynthetic efficiency and maximal electron transport rate, were [...] Read more.

Anabaena sp. was used to examine the toxicity of exposure to a nano-TiO₂ suspension, Zn²⁺ solution, and mixtures of nano-TiO₂ and Zn²⁺ suspensions. Typical chlorophyll fluorescence parameters, including effective quantum yield, photosynthetic efficiency and maximal electron transport rate, were measured by a pulse-amplitude modulated fluorometer. Nano-TiO₂ particles exhibited no significant toxicity at concentrations lower than 10.0 mg/L. The 96 h concentration for the 50% maximal effect (EC₅₀) of Zn²⁺ alone to Anabaena sp. was 0.38 ± 0.004 mg/L. The presence of nano-TiO₂ at low concentrations (<1.0 mg/L) significantly enhanced the toxicity of Zn²⁺ and consequently reduced the EC₅₀ value to 0.29 ± 0.003 mg/L. However, the toxicity of the Zn²⁺/TiO₂ system decreased with increasing nano-TiO₂ concentration because of the substantial adsorption of Zn²⁺ by nano-TiO₂. The toxicity curve of the Zn²⁺/TiO₂ system as a function of incremental nano-TiO₂ concentrations was parabolic. The toxicity significantly increased at the initial stage, reached its maximum, and then decreased with increasing nano-TiO₂ concentration. Hydrodynamic sizes, concentration of nano-TiO₂ and Zn²⁺ loaded nano-TiO₂ were the main parameters for synergistic toxicity. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2013)

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Voltammetry as a Tool for Characterization of CdTe Quantum Dots

by Pavlina Sobrova, Marketa Ryvolova, Jaromir Hubalek, Vojtech Adam and Rene Kizek

Int. J. Mol. Sci. 2013, 14(7), 13497-13510; https://doi.org/10.3390/ijms140713497 - 27 Jun 2013

Cited by 25 | Viewed by 7829

Abstract

Electrochemical detection of quantum dots (QDs) has already been used in numerous applications. However, QDs have not been well characterized using voltammetry, with respect to their characterization and quantification. Therefore, the main aim was to characterize CdTe QDs using cyclic and differential pulse [...] Read more.

Electrochemical detection of quantum dots (QDs) has already been used in numerous applications. However, QDs have not been well characterized using voltammetry, with respect to their characterization and quantification. Therefore, the main aim was to characterize CdTe QDs using cyclic and differential pulse voltammetry. The obtained peaks were identified and the detection limit (3 S/N) was estimated down to 100 fg/mL. Based on the convincing results, a new method for how to study stability and quantify the dots was suggested. Thus, the approach was further utilized for the testing of QDs stability. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2013)

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Open AccessArticle

Non-Covalent Synthesis of Metal Oxide Nanoparticle–Heparin Hybrid Systems: A New Approach to Bioactive Nanoparticles

by Elena Vismara, Antonio Valerio, Alessia Coletti, Giangiacomo Torri, Sabrina Bertini, Giorgio Eisele, Rosalba Gornati and Giovanni Bernardini

Int. J. Mol. Sci. 2013, 14(7), 13463-13481; https://doi.org/10.3390/ijms140713463 - 27 Jun 2013

Cited by 18 | Viewed by 9546

Abstract

Heparin has been conjugated to Fe₃O₄, Co₃O₄, and NiO nanoparticles (NPs) through electrostatic interactions, producing colloidal suspensions of hybrid metal oxide heparin NPs that are stable in water. Negative zeta potentials and retention of heparin’s [...] Read more.

Heparin has been conjugated to Fe₃O₄, Co₃O₄, and NiO nanoparticles (NPs) through electrostatic interactions, producing colloidal suspensions of hybrid metal oxide heparin NPs that are stable in water. Negative zeta potentials and retention of heparin’s ability to capture toluidine blue indicate that heparin’s negative charges are exposed on the surface of the coated NPs. IR results confirmed the formation of nanohybrids as did NMR experiments, which were also interpreted on the basis of toluidine blue tests. Transmission electron microscopy results revealed that the heparin coating does not modify the shape or dimension of the NPs. Dynamic light scattering and negative zeta potential measurements confirmed that heparin surface functionalisation is an effective strategy to prevent NP aggregation. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2013)

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Open AccessArticle

An Ultrasensitive Electrochemiluminescence Immunoassay for Carbohydrate Antigen 19-9 in Serum Based on Antibody Labeled Fe₃O₄ Nanoparticles as Capture Probes and Graphene/CdTe Quantum Dot Bionanoconjugates as Signal Amplifiers

by Ning Gan, Jing Zhou, Ping Xiong, Tianhua Li, Shan Jiang, Yuting Cao and Qianli Jiang

Int. J. Mol. Sci. 2013, 14(5), 10397-10411; https://doi.org/10.3390/ijms140510397 - 17 May 2013

Cited by 18 | Viewed by 10229

Abstract

The CdTe quantum dots (QDs), graphene nanocomposite (CdTe-G) and dextran–Fe₃O₄ magnetic nanoparticles have been synthesized for developing an ultrasensitive electrochemiluminescence (ECL) immunoassay for Carcinoembryonic antigen 19-9 (CA 19-9) in serums. Firstly, the capture probes (CA 19-9 Ab1/Fe₃O₄ [...] Read more.

The CdTe quantum dots (QDs), graphene nanocomposite (CdTe-G) and dextran–Fe₃O₄ magnetic nanoparticles have been synthesized for developing an ultrasensitive electrochemiluminescence (ECL) immunoassay for Carcinoembryonic antigen 19-9 (CA 19-9) in serums. Firstly, the capture probes (CA 19-9 Ab1/Fe₃O₄) for enriching CA 19-9 were synthesized by immobilizing the CA 19-9’s first antibody (CA 19-9 Ab1) on magnetic nanoparticles (dextran-Fe₃O₄). Secondly, the signal probes (CA 19-9 Ab2/CdTe-G), which can emit an ECL signal, were formed by attaching the secondary CA 19-9 antibody (CA 19-9 Ab2) to the surface of the CdTe-G. Thirdly, the above two probes were used for conjugating with a serial of CA 19-9 concentrations. Graphene can immobilize dozens of CdTe QDs on their surface, which can emit stronger ECL intensity than CdTe QDs. Based on the amplified signal, ultrasensitive antigen detection can be realized. Under the optimal conditions, the ECL signal depended linearly on the logarithm of CA 19-9 concentration from 0.005 to 100 pg/mL, and the detection limit was 0.002 pg/mL. Finally, five samples of human serum were tested, and the results were compared with a time-resolved fluorescence assay (TRFA). The novel immunoassay provides a stable, specific and highly sensitive immunoassay protocol for tumor marker detection at very low levels, which can be applied in early diagnosis of tumor. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2013)

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Growth and Potential Damage of Human Bone-Derived Cells on Fresh and Aged Fullerene C₆₀ Films

by Ivana Kopova, Lucie Bacakova, Vasily Lavrentiev and Jiri Vacik

Int. J. Mol. Sci. 2013, 14(5), 9182-9204; https://doi.org/10.3390/ijms14059182 - 26 Apr 2013

Cited by 28 | Viewed by 9411

Abstract

Fullerenes are nanoparticles composed of carbon atoms arranged in a spherical hollow cage-like structure. Numerous studies have evaluated the therapeutic potential of fullerene derivates against oxidative stress-associated conditions, including the prevention or treatment of arthritis. On the other hand, fullerenes are not only [...] Read more.

Fullerenes are nanoparticles composed of carbon atoms arranged in a spherical hollow cage-like structure. Numerous studies have evaluated the therapeutic potential of fullerene derivates against oxidative stress-associated conditions, including the prevention or treatment of arthritis. On the other hand, fullerenes are not only able to quench, but also to generate harmful reactive oxygen species. The reactivity of fullerenes may change in time due to the oxidation and polymerization of fullerenes in an air atmosphere. In this study, we therefore tested the dependence between the age of fullerene films (from one week to one year) and the proliferation, viability and metabolic activity of human osteosarcoma cells (lines MG-63 and U-2 OS). We also monitored potential membrane and DNA damage and morphological changes of the cells. After seven days of cultivation, we did not observe any cytotoxic morphological changes, such as enlarged cells or cytosolic vacuole formation. Furthermore, there was no increased level of DNA damage. The increasing age of the fullerene films did not cause enhancement of cytotoxicity. On the contrary, it resulted in an improvement in the properties of these materials, which are more suitable for cell cultivation. Therefore, fullerene films could be considered as a promising material with potential use as a bioactive coating of cell carriers for bone tissue engineering. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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Magnetic Drug Targeting Reduces the Chemotherapeutic Burden on Circulating Leukocytes

by Christina Janko, Stephan Dürr, Luis E. Munoz, Stefan Lyer, Ricardo Chaurio, Rainer Tietze, Sarah Von Löhneysen, Christine Schorn, Martin Herrmann and Christoph Alexiou

Int. J. Mol. Sci. 2013, 14(4), 7341-7355; https://doi.org/10.3390/ijms14047341 - 2 Apr 2013

Cited by 55 | Viewed by 9394

Abstract

Magnetic drug targeting (MDT) improves the integrity of healthy tissues and cells during treatment with cytotoxic drugs. An anticancer drug is bound to superparamagnetic iron oxide nanoparticles (SPION), injected into the vascular supply of the tumor and directed into the tumor by means [...] Read more.

Magnetic drug targeting (MDT) improves the integrity of healthy tissues and cells during treatment with cytotoxic drugs. An anticancer drug is bound to superparamagnetic iron oxide nanoparticles (SPION), injected into the vascular supply of the tumor and directed into the tumor by means of an external magnetic field. In this study, we investigated the impact of SPION, mitoxantrone (MTO) and SPION^MTO on cell viability in vitro and the nonspecific uptake of MTO into circulating leukocytes in vivo. MDT was compared with conventional chemotherapy. MTO uptake and the impact on cell viability were assessed by flow cytometry in a Jurkat cell culture. In order to analyze MTO loading of circulating leukocytes in vivo, we treated tumor-bearing rabbits with MDT and conventional chemotherapy. In vitro experiments showed a dose-dependent MTO uptake and reduction in the viability and proliferation of Jurkat cells. MTO and SPION^MTO showed similar cytotoxic activity. Non-loaded SPION did not have any effect on cell viability in the concentrations tested. Compared with systemic administration in vivo, MDT employing SPION^MTO significantly decreased the chemotherapeutic load in circulating leukocytes. We demonstrated that MDT spares the immune system in comparison with conventional chemotherapy. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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Trends in Nanopharmaceutical Patents

by Adelaide Antunes, Iolanda Fierro, Rafaela Guerrante, Flavia Mendes and Maria Simone de M. Alencar

Int. J. Mol. Sci. 2013, 14(4), 7016-7031; https://doi.org/10.3390/ijms14047016 - 27 Mar 2013

Cited by 12 | Viewed by 7783

Abstract

Investment in nanotechnology is now a given constant by governments, research centers and companies in both more developed countries and emerging markets. Due to their characteristics, such as high stability, ability to enable antigen identification on specific cells in the human body and [...] Read more.

Investment in nanotechnology is now a given constant by governments, research centers and companies in both more developed countries and emerging markets. Due to their characteristics, such as high stability, ability to enable antigen identification on specific cells in the human body and controlling the release of drugs and, therefore, improving therapies, nanoparticles have been the subject of research and patent applications in the pharmaceutical field. According to the Organization for Economic Co-operation and Development (OCDE), patent data can be used as a source of information in order to measure science and technology activities. Thereby, this paper presents an analysis based on patent documents related to nanotechnology in the pharmaceutical sector. As a result, the analysis of patents demonstrate primarily that nanobiotechnology attracts high levels of R&D investments, including nanoparticle-based chemotherapeutic agents/drugs, monoclonal antibody nanoparticle complexes and their role in drug delivery or contrast agents with non-toxic effects. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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Active Silver Nanoparticles for Wound Healing

by Chiara Rigo, Letizia Ferroni, Ilaria Tocco, Marco Roman, Ivan Munivrana, Chiara Gardin, Warren R. L. Cairns, Vincenzo Vindigni, Bruno Azzena, Carlo Barbante and Barbara Zavan

Int. J. Mol. Sci. 2013, 14(3), 4817-4840; https://doi.org/10.3390/ijms14034817 - 1 Mar 2013

Cited by 249 | Viewed by 20456

Abstract

In this preliminary study, the silver nanoparticle (Ag NP)-based dressing, Acticoat™ Flex 3, has been applied to a 3D fibroblast cell culture in vitro and to a real partial thickness burn patient. The in vitro results show that Ag NPs greatly reduce mitochondrial [...] Read more.

In this preliminary study, the silver nanoparticle (Ag NP)-based dressing, Acticoat™ Flex 3, has been applied to a 3D fibroblast cell culture in vitro and to a real partial thickness burn patient. The in vitro results show that Ag NPs greatly reduce mitochondrial activity, while cellular staining techniques show that nuclear integrity is maintained, with no signs of cell death. For the first time, transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry (ICP-MS) analyses were carried out on skin biopsies taken from a single patient during treatment. The results show that Ag NPs are released as aggregates and are localized in the cytoplasm of fibroblasts. No signs of cell death were observed, and the nanoparticles had different distributions within the cells of the upper and lower dermis. Depth profiles of the Ag concentrations were determined along the skin biopsies. In the healed sample, most of the silver remained in the surface layers, whereas in the unhealed sample, the silver penetrated more deeply. The Ag concentrations in the cell cultures were also determined. Clinical observations and experimental data collected here are consistent with previously published articles and support the safety of Ag NP-based dressing in wound treatment. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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Preparation of Chitosan and Water-Soluble Chitosan Microspheres via Spray-Drying Method to Lower Blood Lipids in Rats Fed with High-Fat Diets

by Yi Tao, Hong-Liang Zhang, Yin-Ming Hu, Shuo Wan and Zheng-Quan Su

Int. J. Mol. Sci. 2013, 14(2), 4174-4184; https://doi.org/10.3390/ijms14024174 - 19 Feb 2013

Cited by 52 | Viewed by 10129

Abstract

This experiment aimed to investigate the effects of the chitosan (CTS) and water-soluble chitosan (WSC) microspheres on plasma lipids in male Sprague-Dawley rats fed with high-fat diets. CTS microspheres and WSC microspheres were prepared by the spray-drying technique. Scanning electron microscopy (SEM) micrographs [...] Read more.

This experiment aimed to investigate the effects of the chitosan (CTS) and water-soluble chitosan (WSC) microspheres on plasma lipids in male Sprague-Dawley rats fed with high-fat diets. CTS microspheres and WSC microspheres were prepared by the spray-drying technique. Scanning electron microscopy (SEM) micrographs showed that the microspheres were nearly spherical in shape. The mean size of CTS microspheres was 4.07 μm (varying from 1.50 to 7.21 μm) and of WSC microspheres was 2.00 μm (varying from 0.85 to 3.58 μm). The rats were classified into eight groups (n = 8) and were fed with high-fat diets for two weeks to establish the hyperlipidemic condition and were then treated with CTS microspheres and WSC microspheres, CTS and WSC for four weeks. The results showed that CTS and WSC microspheres reduced blood lipids and plasma viscosity and increased the serum superoxide dismutase (SOD) levels significantly. This study is the first report of the lipid-lowering effects of CTS and WSC microspheres. CTS and WSC microspheres were found to be more effective in improving hyperlipidemia in rats than common CTS and WSC. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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Cytotoxicity and Genotoxicity of Ceria Nanoparticles on Different Cell Lines in Vitro

by Laura De Marzi, Antonina Monaco, Joaquin De Lapuente, David Ramos, Miquel Borras, Mario Di Gioacchino, Sandro Santucci and Anna Poma

Int. J. Mol. Sci. 2013, 14(2), 3065-3077; https://doi.org/10.3390/ijms14023065 - 1 Feb 2013

Cited by 154 | Viewed by 10257

Abstract

Owing to their radical scavenging and UV-filtering properties, ceria nanoparticles (CeO₂-NPs) are currently used for various applications, including as catalysts in diesel particulate filters. Because of their ability to filter UV light, CeO₂-NPs have garnered significant interest in the [...] Read more.

Owing to their radical scavenging and UV-filtering properties, ceria nanoparticles (CeO₂-NPs) are currently used for various applications, including as catalysts in diesel particulate filters. Because of their ability to filter UV light, CeO₂-NPs have garnered significant interest in the medical field and, consequently, are poised for use in various applications. The aim of this work was to investigate the effects of short-term (24 h) and long-term (10 days) CeO₂-NP exposure to A549, CaCo2 and HepG2 cell lines. Cytotoxicity assays tested CeO₂-NPs over a concentration range of 0.5 μg/mL to 5000 μg/mL, whereas genotoxicity assays tested CeO₂-NPs over a concentration range of 0.5 μg/mL to 5000 μg/mL. In vitro assays showed almost no short-term exposure toxicity on any of the tested cell lines. Conversely, long-term CeO₂-NP exposure proved toxic for all tested cell lines. NP genotoxicity was detectable even at 24-h exposure. HepG2 was the most sensitive cell line overall; however, the A549 line was most sensitive to the lowest concentration tested. Moreover, the results confirmed the ceria nanoparticles’ capacity to protect cells when they are exposed to well-known oxidants such as H₂O₂. A Comet assay was performed in the presence of both H₂O₂ and CeO₂-NPs. When hydrogen peroxide was maintained at 25 μM, NPs at 0.5 μg/mL, 50 μg/mL, and 500 μg/mL protected the cells from oxidative damage. Thus, the NPs prevented H₂O₂-induced genotoxic damage. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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In Vitro and in Vivo Evaluation of Lactoferrin-Conjugated Liposomes as a Novel Carrier to Improve the Brain Delivery

by Feng-Yun J. Huang, Wan-Jou Chen, Wan-Yu Lee, Su-Tang Lo, Te-Wei Lee and Jem-Mau Lo

Int. J. Mol. Sci. 2013, 14(2), 2862-2874; https://doi.org/10.3390/ijms14022862 - 29 Jan 2013

Cited by 77 | Viewed by 8693

Abstract

In this study, lactoferrin-conjugated PEGylated liposomes (PL), a potential drug carrier for brain delivery, was loaded with radioisotope complex, ^99mTc labeled N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (^99mTc-BMEDA) for in vitro and in vivo evaluations. The hydrophilicity of [...] Read more.

In this study, lactoferrin-conjugated PEGylated liposomes (PL), a potential drug carrier for brain delivery, was loaded with radioisotope complex, ^99mTc labeled N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (^99mTc-BMEDA) for in vitro and in vivo evaluations. The hydrophilicity of liposomes was enhanced by PEGylation which was not an ideal brain delivery system for crossing the blood brain barrier (BBB). With the modification of a brain-targeting ligand, lactoferrin (Lf), the PEGylated liposome (PL) might become a potential brain delivery vehicle. In order to test the hypothesis in vitro and in vivo, ^99mTc-BMEDA was loaded into the liposomes as a reporter with or without Lf-conjugation. The mouse brain endothelia cell line, bEnd.3 cells, was cultured to investigate the potential uptake of liposomes in vitro. The in vivo uptake by the mouse brain of the liposomes was detected by tissue biodistribution study. The results indicated that Lf-conjugated PEGylated liposome showed more than three times better uptake efficiency in vitro and two-fold higher of brain uptake in vivo than PEGlyated liposome. With the success of loading the potential Single Photon Emission Tomography (SPECT) imaging probe, ^99mTc-BMEDA, Lf-PL might serve as a promising brain delivery system for loading diagnostics or therapeutics of various brain disorders. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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Comparative in Vivo Assessment of Some Adverse Bioeffects of Equidimensional Gold and Silver Nanoparticles and the Attenuation of Nanosilver’s Effects with a Complex of Innocuous Bioprotectors

by Boris A. Katsnelson, Larisa I. Privalova, Vladimir B. Gurvich, Oleg H. Makeyev, Vladimir Ya. Shur, Yakov B. Beikin, Marina P. Sutunkova, Ekaterina P. Kireyeva, Ilzira A. Minigalieva, Nadezhda V. Loginova, Marina S. Vasilyeva, Artem V. Korotkov, Eugene A. Shuman, Larisa A. Vlasova, Ekaterina V. Shishkina, Anastasia E. Tyurnina, Roman V. Kozin, Irene E. Valamina, Svetlana V. Pichugova and Ludmila G. Tulakina

Int. J. Mol. Sci. 2013, 14(2), 2449-2483; https://doi.org/10.3390/ijms14022449 - 25 Jan 2013

Cited by 63 | Viewed by 11140

Abstract

Stable suspensions of nanogold (NG) and nanosilver (NS) with mean particle diameter 50 and 49 nm, respectively, were prepared by laser ablation of metals in water. To assess rat’s pulmonary phagocytosis response to a single intratracheal instillation of these suspensions, we used optical, [...] Read more.

Stable suspensions of nanogold (NG) and nanosilver (NS) with mean particle diameter 50 and 49 nm, respectively, were prepared by laser ablation of metals in water. To assess rat’s pulmonary phagocytosis response to a single intratracheal instillation of these suspensions, we used optical, transmission electron, and semi-contact atomic force microscopy. NG and NS were also repeatedly injected intraperitoneally into rats at a dose of 10 mg/kg (0.5 mg per mL of deionized water) three times a week, up to 20 injections. A group of rats was thus injected with NS after oral administration of a “bioprotective complex” (BPC) comprised of pectin, multivitamins, some amino acids, calcium, selenium, and omega-3 PUFA. After the termination of the injections, many functional and biochemical indices and histopathological features of the spleen, kidneys and liver were evaluated for signs of toxicity, and accumulation of NG or NS in these organs was measured. From the same rats, we obtained cell suspensions of different tissues for performing the RAPD test. It was demonstrated that, although both nanometals were adversely bioactive in all respects considered in this study, NS was more noxious as compared with NG, and that the BPC tested by us attenuated both the toxicity and genotoxicity of NS. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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Folate-Equipped Nanolipoplexes Mediated Efficient Gene Transfer into Human Epithelial Cells

by Emmanuel Mornet, Nathalie Carmoy, Céline Lainé, Loïc Lemiègre, Tony Le Gall, Isabelle Laurent, Remi Marianowski, Claude Férec, Pierre Lehn, Thierry Benvegnu and Tristan Montier

Int. J. Mol. Sci. 2013, 14(1), 1477-1501; https://doi.org/10.3390/ijms14011477 - 14 Jan 2013

Cited by 20 | Viewed by 8205

Abstract

Since recombinant viral vectors have been associated with serious side effects, such as immunogenicity and oncogenicity, synthetic delivery systems represent a realistic alternative for achieving efficacy in gene therapy. A major challenge for non-viral nanocarriers is the optimization of transgene expression in the [...] Read more.

Since recombinant viral vectors have been associated with serious side effects, such as immunogenicity and oncogenicity, synthetic delivery systems represent a realistic alternative for achieving efficacy in gene therapy. A major challenge for non-viral nanocarriers is the optimization of transgene expression in the targeted cells. This goal can be achieved by fine-tuning the chemical carriers and the adding specific motifs to promote cellular penetration. Our study focuses on the development of novel folate-based complexes that contain varying quantities of folate motifs. After controlling for their physical properties, neutral folate-modified lipid formulations were compared in vitro to lipoplexes leading to comparable expression levels. In addition, no cytotoxicity was detected, unlike what was observed in the cationic controls. Mechanistically, the delivery of the transgene appeared to be, in part, due to endocytosis mediated by folate receptor targeting. This mechanism was further validated by the observation that adding free folate into the medium decreased luciferase expression by 50%. In vivo transfection with the folate-modified MM18 lipid, containing the highest amount of FA-PEG₅₇₀-diether co-lipid (w:w; 90:10), at a neutral charge ratio, gave luciferase transgene expression. These studies indicate that modification of lipids with folate residues could enhance non-toxic, cell-specific gene delivery. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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Evaluation of Anti-Inflammatory Drug-Conjugated Silicon Quantum Dots: Their Cytotoxicity and Biological Effect

by Sanshiro Hanada, Kouki Fujioka, Yasuhiro Futamura, Noriyoshi Manabe, Akiyoshi Hoshino and Kenji Yamamoto

Int. J. Mol. Sci. 2013, 14(1), 1323-1334; https://doi.org/10.3390/ijms14011323 - 10 Jan 2013

Cited by 24 | Viewed by 7909

Abstract

Silicon quantum dots (Si-QDs) have great potential for biomedical applications, including their use as biological fluorescent markers and carriers for drug delivery systems. Biologically inert Si-QDs are less toxic than conventional cadmium-based QDs, and can modify the surface of the Si-QD with covalent [...] Read more.

Silicon quantum dots (Si-QDs) have great potential for biomedical applications, including their use as biological fluorescent markers and carriers for drug delivery systems. Biologically inert Si-QDs are less toxic than conventional cadmium-based QDs, and can modify the surface of the Si-QD with covalent bond. We synthesized water-soluble alminoprofen-conjugated Si-QDs (Ap-Si). Alminoprofen is a non-steroid anti-inflammatory drug (NSAID) used as an analgesic for rheumatism. Our results showed that the “silicon drug” is less toxic than the control Si-QD and the original drug. These phenomena indicate that the condensed surface integration of ligand/receptor-type drugs might reduce the adverse interaction between the cells and drug molecules. In addition, the medicinal effect of the Si-QDs (i.e., the inhibition of COX-2 enzyme) was maintained compared to that of the original drug. The same drug effect is related to the integration ratio of original drugs, which might control the binding interaction between COX-2 and the silicon drug. We conclude that drug conjugation with biocompatible Si-QDs is a potential method for functional pharmaceutical drug development. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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In Vitro Cytotoxicity of Fluorescent Silica Nanoparticles Hybridized with Aggregation-Induced Emission Luminogens for Living Cell Imaging

by Yun Xia, Min Li, Tao Peng, Weijie Zhang, Jun Xiong, Qinggang Hu, Zifang Song and Qichang Zheng

Int. J. Mol. Sci. 2013, 14(1), 1080-1092; https://doi.org/10.3390/ijms14011080 - 7 Jan 2013

Cited by 19 | Viewed by 8451

Abstract

Fluorescent silica nanoparticles (FSNPs) can provide high-intensity and photostable fluorescent signals as a probe for biomedical analysis. In this study, FSNPs hybridized with aggregation-induced emission (AIE) luminogens (namely FSNP-SD) were successfully fabricated by a surfactant-free sol-gel method. The FSNP-SD were spherical, monodisperse and [...] Read more.

Fluorescent silica nanoparticles (FSNPs) can provide high-intensity and photostable fluorescent signals as a probe for biomedical analysis. In this study, FSNPs hybridized with aggregation-induced emission (AIE) luminogens (namely FSNP-SD) were successfully fabricated by a surfactant-free sol-gel method. The FSNP-SD were spherical, monodisperse and uniform in size, with an average diameter of approximately 100 nm, and emitted strong fluorescence at the peak of 490 nm. The FSNP-SD selectively stained the cytoplasmic regions and were distributed in the cytoplasm. Moreover, they can stay inside cells, enabling the tacking of cells over a long period of time. The intracellular vesicles and multinucleated cells were increase gradually with the rise of FSNP-SD concentration. Both cell viability and survival only lost less than 20% when the cells were exposed to the high concentration of 100 μg/mL FSNP-SD. Additionally, the cell apoptosis and intracellular ROS assay indicated that FSNP-SD had no significant toxic effects at the maximum working concentration of 80 μg/mL. This study demonstrated that the FSNP-SD are promising biocompatible fluorescent probes for living cell imaging. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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Photodegradable Polyesters for Triggered Release

by Cong Lv, Zhen Wang, Peng Wang and Xinjing Tang

Int. J. Mol. Sci. 2012, 13(12), 16387-16399; https://doi.org/10.3390/ijms131216387 - 3 Dec 2012

Cited by 20 | Viewed by 6965

Abstract

Photodegradable polyesters were synthesized with a photolabile monomer 2-nitrophenylethylene glycol and dioyl chlorides with different lengths. These polymers can be assembled to form polymeric particles with encapsulation of target substances. Light activation can degrade these particles and release payloads in both aqueous solutions [...] Read more.

Photodegradable polyesters were synthesized with a photolabile monomer 2-nitrophenylethylene glycol and dioyl chlorides with different lengths. These polymers can be assembled to form polymeric particles with encapsulation of target substances. Light activation can degrade these particles and release payloads in both aqueous solutions and RAW 264.7 cells. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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Impairment of Coronary Arteriolar Endothelium-Dependent Dilation after Multi-Walled Carbon Nanotube Inhalation: A Time-Course Study

by Phoebe A. Stapleton, Valerie C. Minarchick, Amy M. Cumpston, Walter McKinney, Bean T. Chen, Tina M. Sager, David G. Frazer, Robert R. Mercer, James Scabilloni, Michael E. Andrew, Vincent Castranova and Timothy R. Nurkiewicz

Int. J. Mol. Sci. 2012, 13(11), 13781-13803; https://doi.org/10.3390/ijms131113781 - 24 Oct 2012

Cited by 97 | Viewed by 8210

Abstract

Engineered nanomaterials have been developed for widespread applications due to many highly unique and desirable characteristics. The purpose of this study was to assess pulmonary inflammation and subepicardial arteriolar reactivity in response to multi-walled carbon nanotube (MWCNT) inhalation and evaluate the time course [...] Read more.

Engineered nanomaterials have been developed for widespread applications due to many highly unique and desirable characteristics. The purpose of this study was to assess pulmonary inflammation and subepicardial arteriolar reactivity in response to multi-walled carbon nanotube (MWCNT) inhalation and evaluate the time course of vascular alterations. Rats were exposed to MWCNT aerosols producing pulmonary deposition. Pulmonary inflammation via bronchoalveolar lavage and MWCNT translocation from the lungs to systemic organs was evident 24 h post-inhalation. Coronary arterioles were evaluated 24–168 h post-exposure to determine microvascular response to changes in transmural pressure, endothelium-dependent and -independent reactivity. Myogenic responsiveness, vascular smooth muscle reactivity to nitric oxide, and α-adrenergic responses all remained intact. However, a severe impact on endothelium-dependent dilation was observed within 24 h after MWCNT inhalation, a condition which improved, but did not fully return to control after 168 h. In conclusion, results indicate that MWCNT inhalation not only leads to pulmonary inflammation and cytotoxicity at low lung burdens, but also a low level of particle translocation to systemic organs. MWCNT inhalation also leads to impairments of endothelium-dependent dilation in the coronary microcirculation within 24 h, a condition which does not fully dissipate within 168 h. The innovations within the field of nanotechnology, while exciting and novel, can only reach their full potential if toxicity is first properly assessed. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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Cytotoxicity of Phenol Red in Toxicity Assays for Carbon Nanoparticles

by Ying Zhu, Xiaoyong Zhang, Jianhua Zhu, Qunfen Zhao, Yuguo Li, Wenxin Li, Chunhai Fan and Qing Huang

Int. J. Mol. Sci. 2012, 13(10), 12336-12348; https://doi.org/10.3390/ijms131012336 - 26 Sep 2012

Cited by 36 | Viewed by 9107

Abstract

To explore the novel properties of carbon nanoparticles (CNPs) in nanotoxicity assays, the adsorption of phenol red (a pH indicator for culture medium) by multi-walled carbon nanotubes (MWNTs) and three kinds of carbon blacks (CBs) with nanosize, and its effects on cytotoxicity were [...] Read more.

To explore the novel properties of carbon nanoparticles (CNPs) in nanotoxicity assays, the adsorption of phenol red (a pH indicator for culture medium) by multi-walled carbon nanotubes (MWNTs) and three kinds of carbon blacks (CBs) with nanosize, and its effects on cytotoxicity were studied. Results indicated that the phenol red adsorbed and delivered into cells by CBs was responsible for the toxicity to Hela cells in the medium without serum. The cellular uptake of phenol red was verified using ¹²⁵I-labeling techniques. The size-dependent cytotoxicity of CBs was found to closely correlate to adsorption of phenol red, cellular uptake of phenol red-CB complexes and the amount of phenol red delivered into the cells by CBs. Although the CBs were either nontoxic or slightly toxic, as vehicles of phenol red, they played an essential role in the cytotoxicity induced by phenol red. However, MWNTs showed an intrinsic cytotoxicity independent of phenol red. The implications associated with these findings are discussed. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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Open AccessArticle

Cellular Delivery of Doxorubicin via pH-Controlled Hydrazone Linkage Using Multifunctional Nano Vehicle Based on Poly(β-L-Malic Acid)

by Rameshwar Patil, Jose Portilla-Arias, Hui Ding, Bindu Konda, Arthur Rekechenetskiy, Satoshi Inoue, Keith L. Black, Eggehard Holler and Julia Y. Ljubimova

Int. J. Mol. Sci. 2012, 13(9), 11681-11693; https://doi.org/10.3390/ijms130911681 - 17 Sep 2012

Cited by 74 | Viewed by 14286

Abstract

Doxorubicin (DOX) is currently used in cancer chemotherapy to treat many tumors and shows improved delivery, reduced toxicity and higher treatment efficacy when being part of nanoscale delivery systems. However, a major drawback remains its toxicity to healthy tissue and the development of [...] Read more.

Doxorubicin (DOX) is currently used in cancer chemotherapy to treat many tumors and shows improved delivery, reduced toxicity and higher treatment efficacy when being part of nanoscale delivery systems. However, a major drawback remains its toxicity to healthy tissue and the development of multi-drug resistance during prolonged treatment. This is why in our work we aimed to improve DOX delivery and reduce the toxicity by chemical conjugation with a new nanoplatform based on polymalic acid. For delivery into recipient cancer cells, DOX was conjugated via pH-sensitive hydrazone linkage along with polyethylene glycol (PEG) to a biodegradable, non-toxic and non-immunogenic nanoconjugate platform: poly(β-L-malic acid) (PMLA). DOX-nanoconjugates were found stable under physiological conditions and shown to successfully inhibit in vitro cancer cell growth of several invasive breast carcinoma cell lines such as MDA-MB-231 and MDA-MB- 468 and of primary glioma cell lines such as U87MG and U251. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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Open AccessArticle

Structural and Oxidative Changes in the Kidney of Crucian Carp Induced by Silicon-Based Quantum Dots

by Sorina Nicoleta Petrache, Loredana Stanca, Andreea Iren Serban, Cornelia Sima, Andreia Cristina Staicu, Maria Cristina Munteanu, Marieta Costache, Radu Burlacu, Otilia Zarnescu and Anca Dinischiotu

Int. J. Mol. Sci. 2012, 13(8), 10193-10211; https://doi.org/10.3390/ijms130810193 - 16 Aug 2012

Cited by 19 | Viewed by 9274

Abstract

Silicon-based quantum dots were intraperitoneally injected in Carassius auratus gibelio specimens and, over one week, the effects on renal tissue were investigated by following their distribution and histological effects, as well as antioxidative system modifications. After three and seven days, detached epithelial cells [...] Read more.

Silicon-based quantum dots were intraperitoneally injected in Carassius auratus gibelio specimens and, over one week, the effects on renal tissue were investigated by following their distribution and histological effects, as well as antioxidative system modifications. After three and seven days, detached epithelial cells from the basal lamina, dilated tubules and debris in the lumen of tubules were observed. At day 7, nephrogenesis was noticed. The reduced glutathione (GSH) concentration decreased in the first three days and started to rise later on. The superoxide dismutase (SOD) activity increased only after one week, whereas catalase (CAT) was up-regulated in a time-dependent manner. The activities of glutathione reductase (GR) and glutathione peroxidise (GPX) decreased dramatically by approximately 50% compared to control, whereas the glutathione-S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PDH) increased significantly after 3 and 7 days of treatment. Oxidative modifications of proteins and the time-dependent increase of Hsp70 expression were also registered. Our data suggest that silicon-based quantum dots induced oxidative stress followed by structural damages. However, renal tissue is capable of restoring its integrity by nephron development. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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Green Synthesis of Silver Nanoparticles through Reduction with Solanum xanthocarpum L. Berry Extract: Characterization, Antimicrobial and Urease Inhibitory Activities against Helicobacter pylori

by Muhammad Amin, Farooq Anwar, Muhammad Ramzan Saeed Ashraf Janjua, Muhammad Awais Iqbal and Umer Rashid

Int. J. Mol. Sci. 2012, 13(8), 9923-9941; https://doi.org/10.3390/ijms13089923 - 9 Aug 2012

Cited by 308 | Viewed by 19052

Abstract

A green synthesis route for the production of silver nanoparticles using methanol extract from Solanum xanthocarpum berry (SXE) is reported in the present investigation. Silver nanoparticles (AgNps), having a surface plasmon resonance (SPR) band centered at 406 nm, were synthesized by reacting SXE [...] Read more.

A green synthesis route for the production of silver nanoparticles using methanol extract from Solanum xanthocarpum berry (SXE) is reported in the present investigation. Silver nanoparticles (AgNps), having a surface plasmon resonance (SPR) band centered at 406 nm, were synthesized by reacting SXE (as capping as well as reducing agent) with AgNO₃ during a 25 min process at 45 °C. The synthesized AgNps were characterized using UV–Visible spectrophotometry, powdered X-ray diffraction, and transmission electron microscopy (TEM). The results showed that the time of reaction, temperature and volume ratio of SXE to AgNO₃ could accelerate the reduction rate of Ag⁺ and affect the AgNps size and shape. The nanoparticles were found to be about 10 nm in size, mono-dispersed in nature, and spherical in shape. In vitro anti-Helicobacter pylori activity of synthesized AgNps was tested against 34 clinical isolates and two reference strains of Helicobacter pylori by the agar dilution method and compared with AgNO₃ and four standard drugs, namely amoxicillin (AMX), clarithromycin (CLA), metronidazole (MNZ) and tetracycline (TET), being used in anti-H. pylori therapy. Typical AgNps sample (S1) effectively inhibited the growth of H. pylori, indicating a stronger anti-H. pylori activity than that of AgNO₃ or MNZ, being almost equally potent to TET and less potent than AMX and CLA. AgNps under study were found to be equally efficient against the antibiotic-resistant and antibiotic-susceptible strains of H. pylori. Besides, in the H. pylori urease inhibitory assay, S1 also exhibited a significant inhibition. Lineweaver-Burk plots revealed that the mechanism of inhibition was noncompetitive. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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Open AccessArticle

Fabrication, Modeling and Characterization of Multi-Crosslinked Methacrylate Copolymeric Nanoparticles for Oral Drug Delivery

by Ndidi C. Ngwuluka, Viness Pillay, Yahya E. Choonara, Girish Modi, Dinesh Naidoo, Lisa C. du Toit, Pradeep Kumar, Valence M.K. Ndesendo and Riaz A. Khan

Int. J. Mol. Sci. 2011, 12(9), 6194-6225; https://doi.org/10.3390/ijms12096194 - 23 Sep 2011

Cited by 20 | Viewed by 9753

Abstract

Nanotechnology remains the field to explore in the quest to enhance therapeutic efficacies of existing drugs. Fabrication of a methacrylate copolymer-lipid nanoparticulate (MCN) system was explored in this study for oral drug delivery of levodopa. The nanoparticles were fabricated employing multicrosslinking technology and [...] Read more.

Nanotechnology remains the field to explore in the quest to enhance therapeutic efficacies of existing drugs. Fabrication of a methacrylate copolymer-lipid nanoparticulate (MCN) system was explored in this study for oral drug delivery of levodopa. The nanoparticles were fabricated employing multicrosslinking technology and characterized for particle size, zeta potential, morphology, structural modification, drug entrapment efficiency and in vitro drug release. Chemometric Computational (CC) modeling was conducted to deduce the mechanism of nanoparticle synthesis as well as to corroborate the experimental findings. The CC modeling deduced that the nanoparticles synthesis may have followed the mixed triangular formations or the mixed patterns. They were found to be hollow nanocapsules with a size ranging from 152 nm (methacrylate copolymer) to 321 nm (methacrylate copolymer blend) and a zeta potential range of 15.8–43.3 mV. The nanoparticles were directly compressible and it was found that the desired rate of drug release could be achieved by formulating the nanoparticles as a nanosuspension, and then directly compressing them into tablet matrices or incorporating the nanoparticles directly into polymer tablet matrices. However, sustained release of MCNs was achieved only when it was incorporated into a polymer matrix. The experimental results were well corroborated by the CC modeling. The developed technology may be potentially useful for the fabrication of multi-crosslinked polymer blend nanoparticles for oral drug delivery. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles (special issue))

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Open AccessArticle

Interaction of Human Serum Album and C₆₀ Aggregates in Solution

by Maoyong Song, Shufang Liu, Junfa Yin and Hailin Wang

Int. J. Mol. Sci. 2011, 12(8), 4964-4974; https://doi.org/10.3390/ijms12084964 - 4 Aug 2011

Cited by 57 | Viewed by 8642

Abstract

An important property of C₆₀ in aquatic ecotoxicology is that it can form stable aggregates with nanoscale dimensions, namely nC₆₀. Aggregation allows fullerenes to remain suspended for a long time, and the reactivity of individual C₆₀ is substantially altered [...] Read more.

An important property of C₆₀ in aquatic ecotoxicology is that it can form stable aggregates with nanoscale dimensions, namely nC₆₀. Aggregation allows fullerenes to remain suspended for a long time, and the reactivity of individual C₆₀ is substantially altered in this aggregate form. Herein, we investigated the interaction of nC₆₀ and human serum album (HSA) using the methods of fluorescence, fluorescence dynamics, circular dichroism (CD), and site marker competitive experiments. We proposed a binding model consistent with the available experimental results for the interactions of nC₆₀ with HSA. During the interaction process, the structure and conformation of HSA were affected, leading to functional changes of drug binding sites of HSA. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles (special issue))

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Enhanced Anti-Tumoral Activity of Methotrexate-Human Serum Albumin Conjugated Nanoparticles by Targeting with Luteinizing Hormone-Releasing Hormone (LHRH) Peptide

by Azade Taheri, Rassoul Dinarvand, Fatemeh Atyabi, Fatemeh Ahadi, Farank Salman Nouri, Mohammad Hossein Ghahremani, Seyed Nasser Ostad, Atefeh Taheri Borougeni and Pooria Mansoori

Int. J. Mol. Sci. 2011, 12(7), 4591-4608; https://doi.org/10.3390/ijms12074591 - 15 Jul 2011

Cited by 47 | Viewed by 10048

Abstract

Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA) conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH) as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in [...] Read more.

Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA) conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH) as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120–138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles (special issue))

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A Novel Preparation Method for Camptothecin (CPT) Loaded Folic Acid Conjugated Dextran Tumor-Targeted Nanoparticles

by Yuangang Zu, Dan Wang, Xiuhua Zhao, Ru Jiang, Qi Zhang, Dongmei Zhao, Yong Li, Baishi Zu and Zhiqiang Sun

Int. J. Mol. Sci. 2011, 12(7), 4237-4249; https://doi.org/10.3390/ijms12074237 - 28 Jun 2011

Cited by 39 | Viewed by 11099

Abstract

In this study, folic-dextran-camptothecin (Fa-DEX-CPT) tumor-targeted nanoparticles were produced with a supercritical antisolvent (SAS) technique by using dimethyl sulfoxide (DMSO) as a solvent and carbon dioxide as an antisolvent. A factorial design was used to reveal the effect of various process parameters on [...] Read more.

In this study, folic-dextran-camptothecin (Fa-DEX-CPT) tumor-targeted nanoparticles were produced with a supercritical antisolvent (SAS) technique by using dimethyl sulfoxide (DMSO) as a solvent and carbon dioxide as an antisolvent. A factorial design was used to reveal the effect of various process parameters on the mean particle size (MPS) and morphology of the particles formed. Under the optimum operation conditions, Fa-DEX-CPT nanoparticles with a MPS of 182.21 nm were obtained. Drug encapsulation efficiency and loading efficiency were 62.13% and 36.12%, respectively. It was found that the concentrations of the camptothecin (CPT) and dextran solution had a major influence upon morphology and shape of the final product. In addition, the samples were characterized by Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) with the purpose of developing a suitable targeted drug delivery system for cancer chemotherapy. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles (special issue))

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Release of Bacteriocins from Nanofibers Prepared with Combinations of Poly(D,L-lactide) (PDLLA) and Poly(Ethylene Oxide) (PEO)

by Tiaan Heunis, Osama Bshena, Bert Klumperman and Leon Dicks

Int. J. Mol. Sci. 2011, 12(4), 2158-2173; https://doi.org/10.3390/ijms12042158 - 29 Mar 2011

Cited by 77 | Viewed by 10733

Abstract

Plantaricin 423, produced by Lactobacillus plantarum, and bacteriocin ST4SA produced by Enterococcus mundtii, were electrospun into nanofibers prepared from different combinations of poly(D,L-lactide) (PDLLA) and poly(ethylene oxide) (PEO) dissolved in N,N-dimethylformamide (DMF). Both peptides were released from the [...] Read more.

Plantaricin 423, produced by Lactobacillus plantarum, and bacteriocin ST4SA produced by Enterococcus mundtii, were electrospun into nanofibers prepared from different combinations of poly(D,L-lactide) (PDLLA) and poly(ethylene oxide) (PEO) dissolved in N,N-dimethylformamide (DMF). Both peptides were released from the nanofibers with a high initial burst and retained 88% of their original antimicrobial activity at 37 °C. Nanofibers have the potential to serve as carrier matrix for bacteriocins and open a new field in developing controlled antimicrobial delivery systems for various applications. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles (special issue))

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Microscopic Investigation of Reversible Nanoscale Surface Size Dependent Protein Conjugation

by Kazushige Yokoyama, Hyunah Cho, Sean P. Cullen, Matthew Kowalik, Nicole M. Briglio, Harold J. Hoops, Zhouying Zhao and Michael A. Carpenter

Int. J. Mol. Sci. 2009, 10(5), 2348-2366; https://doi.org/10.3390/ijms10052348 - 20 May 2009

Cited by 17 | Viewed by 13095

Abstract

Aβ_1-40 coated 20 nm gold colloidal nanoparticles exhibit a reversible color change as pH is externally altered between pH 4 and 10. This reversible process may contain important information on the initial reversible step reported for the fibrillogenesis of Aβ (a hallmark [...] Read more.

Aβ_1-40 coated 20 nm gold colloidal nanoparticles exhibit a reversible color change as pH is externally altered between pH 4 and 10. This reversible process may contain important information on the initial reversible step reported for the fibrillogenesis of Aβ (a hallmark of Alzheimer’s disease). We examined this reversible color change by microscopic investigations. AFM images on graphite surfaces revealed the morphology of Aβ aggregates with gold colloids. TEM images clearly demonstrate the correspondence between spectroscopic features and conformational changes of the gold colloid. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles (special issue))

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Open AccessArticle

A Novel Method for the Preparation of Retinoic Acid-Loaded Nanoparticles

by Cesare Errico, Matteo Gazzarri and Federica Chiellini

Int. J. Mol. Sci. 2009, 10(5), 2336-2347; https://doi.org/10.3390/ijms10052336 - 19 May 2009

Cited by 13 | Viewed by 11102

Abstract

The goal of present work was to investigate the use of bioerodible polymeric nanoparticles as carriers of retinoic acid (RA), which is known to induce differentiation of several cell lines into neurons. A novel method, named “Colloidal-Coating”, has been developed for the preparation [...] Read more.

The goal of present work was to investigate the use of bioerodible polymeric nanoparticles as carriers of retinoic acid (RA), which is known to induce differentiation of several cell lines into neurons. A novel method, named “Colloidal-Coating”, has been developed for the preparation of nanoparticles based on a copolymer of maleic anhydride and butyl vinyl ether (VAM41) loaded with RA. Nanoparticles with an average diameter size of 70 nm and good morphology were prepared. The activity of the encapsulated RA was evaluated on SK-N-SH human neuroblastoma cells, which are known to undergo inhibition of proliferation and neuronal differentiation upon treatment with RA. The activity of RA was not affected by the encapsulation and purification processes. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles (special issue))

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Review

Jump to: Research, Other

24 pages, 7429 KiB

Open AccessReview

Nanomaterials for Delivering Antibiotics in the Therapy of Pneumonia

by Jie Tang, Qiuhong Ouyang, Yanyan Li, Peisen Zhang, Weihua Jin, Shuang Qu, Fengmei Yang, Zhanlong He and Meng Qin

Int. J. Mol. Sci. 2022, 23(24), 15738; https://doi.org/10.3390/ijms232415738 - 12 Dec 2022

Cited by 12 | Viewed by 6535

Abstract

Bacterial pneumonia is one of the leading causes of death worldwide and exerts a significant burden on health-care resources. Antibiotics have long been used as first-line drugs for the treatment of bacterial pneumonia. However, antibiotic therapy and traditional antibiotic delivery are associated with [...] Read more.

Bacterial pneumonia is one of the leading causes of death worldwide and exerts a significant burden on health-care resources. Antibiotics have long been used as first-line drugs for the treatment of bacterial pneumonia. However, antibiotic therapy and traditional antibiotic delivery are associated with important challenges, including drug resistance, low bioavailability, and adverse side effects; the existence of physiological barriers further hampers treatment. Fortunately, these limitations may be overcome by the application of nanotechnology, which can facilitate drug delivery while improving drug stability and bioavailability. This review summarizes the challenges facing the treatment of bacterial pneumonia and also highlights the types of nanoparticles that can be used for antibiotic delivery. This review places a special focus on the state-of-the-art in nanomaterial-based approaches to the delivery of antibiotics for the treatment of pneumonia. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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16 pages, 4291 KiB

Open AccessReview

Two-Dimensional and Three-Dimensional Single Particle Tracking of Upconverting Nanoparticles in Living Cells

by Kyujin Shin, Yo Han Song, Yeongchang Goh and Kang Taek Lee

Int. J. Mol. Sci. 2019, 20(6), 1424; https://doi.org/10.3390/ijms20061424 - 21 Mar 2019

Cited by 28 | Viewed by 6823

Abstract

Lanthanide-doped upconversion nanoparticles (UCNPs) are inorganic nanomaterials in which the lanthanide cations embedded in the host matrix can convert incident near-infrared light to visible or ultraviolet light. These particles are often used for long-term and real-time imaging because they are extremely stable even [...] Read more.

Lanthanide-doped upconversion nanoparticles (UCNPs) are inorganic nanomaterials in which the lanthanide cations embedded in the host matrix can convert incident near-infrared light to visible or ultraviolet light. These particles are often used for long-term and real-time imaging because they are extremely stable even when subjected to continuous irradiation for a long time. It is now possible to image their movement at the single particle level with a scale of a few nanometers and track their trajectories as a function of time with a scale of a few microseconds. Such UCNP-based single-particle tracking (SPT) technology provides information about the intracellular structures and dynamics in living cells. Thus far, most imaging techniques have been built on fluorescence microscopic techniques (epifluorescence, total internal reflection, etc.). However, two-dimensional (2D) images obtained using these techniques are limited in only being able to visualize those on the focal planes of the objective lens. On the contrary, if three-dimensional (3D) structures and dynamics are known, deeper insights into the biology of the thick cells and tissues can be obtained. In this review, we introduce the status of the fluorescence imaging techniques, discuss the mathematical description of SPT, and outline the past few studies using UCNPs as imaging probes or biologically functionalized carriers. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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17 pages, 1279 KiB

Open AccessReview

Applications of Noble Metal-Based Nanoparticles in Medicine

by Bartosz Klębowski, Joanna Depciuch, Magdalena Parlińska-Wojtan and Jarek Baran

Int. J. Mol. Sci. 2018, 19(12), 4031; https://doi.org/10.3390/ijms19124031 - 13 Dec 2018

Cited by 193 | Viewed by 10520

Abstract

Nanoparticles have unique, size-dependent properties, which means they are widely used in various branches of industry. The ability to control the properties of nanoparticles makes these nanomaterials very interesting for medicine and pharmacology. The application of nanoparticles in medicine is associated with the [...] Read more.

Nanoparticles have unique, size-dependent properties, which means they are widely used in various branches of industry. The ability to control the properties of nanoparticles makes these nanomaterials very interesting for medicine and pharmacology. The application of nanoparticles in medicine is associated with the design of specific nanostructures, which can be used as novel diagnostic and therapeutic modalities. There are a lot of applications of nanoparticles, e.g., as drug delivery systems, radiosensitizers in radiation or proton therapy, in bioimaging, or as bactericides/fungicides. This paper aims to introduce the characteristics of noble metal-based nanoparticles with particular emphasis on their applications in medicine and related sciences. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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18 pages, 1655 KiB

Open AccessReview

Bioactive Nanoparticles for Cancer Immunotherapy

by Suchithra Poilil Surendran, Myeong Ju Moon, Rayoung Park and Yong Yeon Jeong

Int. J. Mol. Sci. 2018, 19(12), 3877; https://doi.org/10.3390/ijms19123877 - 4 Dec 2018

Cited by 87 | Viewed by 9362

Abstract

Currently, immunotherapy is considered to be one of the effective treatment modalities for cancer. All the developments and discoveries in this field up to the recent Nobel Prize add to the interest for research into this vast area of study. Targeting tumor environment [...] Read more.

Currently, immunotherapy is considered to be one of the effective treatment modalities for cancer. All the developments and discoveries in this field up to the recent Nobel Prize add to the interest for research into this vast area of study. Targeting tumor environment as well as the immune system is a suitable strategy to be applied for cancer treatment. Usage of nanoparticle systems for delivery of immunotherapeutic agents to the body being widely studied and found to be a promising area of research to be considered and investigated further. Nanoparticles for immunotherapy would be one of the effective treatment options for cancer therapy in the future due to their high specificity, efficacy, ability to diagnose, imaging, and therapeutic effect. Among the many nanoparticle systems, polylactic-co-glycolic acid (PLGA) nanoparticles, liposomes, micelles, gold nanoparticles, iron oxide, dendrimers, and artificial exosomes are widely used for immunotherapy of cancer. Moreover, the combination therapy found to be the more effective way of treating the tumor. Here, we review the current trends in nanoparticle therapy and efficiency of these nanosystems in delivering antigens, adjuvants, therapeutic drugs, and other immunotherapeutic agents. This review summarizes the currently available bioactive nanoparticle systems for cancer immunotherapy. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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20 pages, 1195 KiB

Open AccessReview

Gold Nanoparticle-Induced Cell Death and Potential Applications in Nanomedicine

by Hainan Sun, Jianbo Jia, Cuijuan Jiang and Shumei Zhai

Int. J. Mol. Sci. 2018, 19(3), 754; https://doi.org/10.3390/ijms19030754 - 7 Mar 2018

Cited by 90 | Viewed by 7331

Abstract

Cell death is crucial to human health and is related to various serious diseases. Therefore, generation of new cell death regulators is urgently needed for disease treatment. Nanoparticles (NPs) are now routinely used in a variety of fields, including consumer products and medicine. [...] Read more.

Cell death is crucial to human health and is related to various serious diseases. Therefore, generation of new cell death regulators is urgently needed for disease treatment. Nanoparticles (NPs) are now routinely used in a variety of fields, including consumer products and medicine. Exhibiting stability and ease of decoration, gold nanoparticles (GNPs) could be used in diagnosis and disease treatment. Upon entering the human body, GNPs contact human cells in the blood, targeting organs and the immune system. This property results in the disturbance of cell function and even cell death. Therefore, GNPs may act as powerful cell death regulators. However, at present, we are far from establishing a structure–activity relationship between the physicochemical properties of GNPs and cell death, and predicting GNP-induced cell death. In this review, GNPs’ size, shape, and surface properties are observed to play key roles in regulating various cell death modalities and related signaling pathways. These results could guide the design of GNPs for nanomedicine. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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27 pages, 4240 KiB

Open AccessReview

Surface Functionalization and Targeting Strategies of Liposomes in Solid Tumor Therapy: A Review

by Muhammad Kashif Riaz, Muhammad Adil Riaz, Xue Zhang, Congcong Lin, Ka Hong Wong, Xiaoyu Chen, Ge Zhang, Aiping Lu and Zhijun Yang

Int. J. Mol. Sci. 2018, 19(1), 195; https://doi.org/10.3390/ijms19010195 - 9 Jan 2018

Cited by 376 | Viewed by 20468

Abstract

Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The phospholipid vesicles (liposomes) containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can [...] Read more.

Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The phospholipid vesicles (liposomes) containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can effectively target the solid tumors. This article reviews information about the strategies for targeting of liposomes to solid tumors along with the possible targets in cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature. Targeting ligands for functionalization of liposomes with relevant surface engineering techniques have been described. Stimuli strategies for enhanced delivery of anticancer agents at requisite location using stimuli-responsive functionalized liposomes have been discussed. Recent approaches for enhanced delivery of anticancer agents at tumor site with relevant surface functionalization techniques have been reviewed. Finally, current challenges of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Open AccessReview

Current Technical Approaches for the Early Detection of Foodborne Pathogens: Challenges and Opportunities

by Il-Hoon Cho and Seockmo Ku

Int. J. Mol. Sci. 2017, 18(10), 2078; https://doi.org/10.3390/ijms18102078 - 30 Sep 2017

Cited by 60 | Viewed by 8398

Abstract

The development of novel and high-tech solutions for rapid, accurate, and non-laborious microbial detection methods is imperative to improve the global food supply. Such solutions have begun to address the need for microbial detection that is faster and more sensitive than existing methodologies [...] Read more.

The development of novel and high-tech solutions for rapid, accurate, and non-laborious microbial detection methods is imperative to improve the global food supply. Such solutions have begun to address the need for microbial detection that is faster and more sensitive than existing methodologies (e.g., classic culture enrichment methods). Multiple reviews report the technical functions and structures of conventional microbial detection tools. These tools, used to detect pathogens in food and food homogenates, were designed via qualitative analysis methods. The inherent disadvantage of these analytical methods is the necessity for specimen preparation, which is a time-consuming process. While some literature describes the challenges and opportunities to overcome the technical issues related to food industry legal guidelines, there is a lack of reviews of the current trials to overcome technological limitations related to sample preparation and microbial detection via nano and micro technologies. In this review, we primarily explore current analytical technologies, including metallic and magnetic nanomaterials, optics, electrochemistry, and spectroscopy. These techniques rely on the early detection of pathogens via enhanced analytical sensitivity and specificity. In order to introduce the potential combination and comparative analysis of various advanced methods, we also reference a novel sample preparation protocol that uses microbial concentration and recovery technologies. This technology has the potential to expedite the pre-enrichment step that precedes the detection process. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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The Current State of Nanoparticle-Induced Macrophage Polarization and Reprogramming Research

by Xiaoyuan Miao, Xiangfeng Leng and Qiu Zhang

Int. J. Mol. Sci. 2017, 18(2), 336; https://doi.org/10.3390/ijms18020336 - 6 Feb 2017

Cited by 156 | Viewed by 14683

Abstract

Macrophages are vital regulators of the host defense in organisms. In response to different local microenvironments, resting macrophages (M0) can be polarized into different phenotypes, pro-inflammatory (M1) or anti-inflammatory (M2), and perform different roles in different physiological or pathological conditions. Polarized macrophages can [...] Read more.

Macrophages are vital regulators of the host defense in organisms. In response to different local microenvironments, resting macrophages (M0) can be polarized into different phenotypes, pro-inflammatory (M1) or anti-inflammatory (M2), and perform different roles in different physiological or pathological conditions. Polarized macrophages can also be further reprogrammed by reversing their phenotype according to the changed milieu. Macrophage polarization and reprogramming play essential roles in maintaining the steady state of the immune system and are involved in the processes of many diseases. As foreign substances, nanoparticles (NPs) mainly target macrophages after entering the body. NPs can perturb the polarization and reprogramming of macrophages, affect their immunological function and, therefore, affect the pathological process of disease. Optimally-designed NPs for the modulation of macrophage polarization and reprogramming might provide new solutions for treating diseases. Systematically investigating how NPs affect macrophage polarization is crucial for understanding the regulatory effects of NPs on immune cells in vivo. In this review, macrophage polarization by NPs is summarized and discussed. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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The Role of Reactive Oxygen Species (ROS) in the Biological Activities of Metallic Nanoparticles

by Ahmed Abdal Dayem, Mohammed Kawser Hossain, Soo Bin Lee, Kyeongseok Kim, Subbroto Kumar Saha, Gwang-Mo Yang, Hye Yeon Choi and Ssang-Goo Cho

Int. J. Mol. Sci. 2017, 18(1), 120; https://doi.org/10.3390/ijms18010120 - 10 Jan 2017

Cited by 813 | Viewed by 41813

Abstract

Nanoparticles (NPs) possess unique physical and chemical properties that make them appropriate for various applications. The structural alteration of metallic NPs leads to different biological functions, specifically resulting in different potentials for the generation of reactive oxygen species (ROS). The amount of ROS [...] Read more.

Nanoparticles (NPs) possess unique physical and chemical properties that make them appropriate for various applications. The structural alteration of metallic NPs leads to different biological functions, specifically resulting in different potentials for the generation of reactive oxygen species (ROS). The amount of ROS produced by metallic NPs correlates with particle size, shape, surface area, and chemistry. ROS possess multiple functions in cellular biology, with ROS generation a key factor in metallic NP-induced toxicity, as well as modulation of cellular signaling involved in cell death, proliferation, and differentiation. In this review, we briefly explained NP classes and their biomedical applications and describe the sources and roles of ROS in NP-related biological functions in vitro and in vivo. Furthermore, we also described the roles of metal NP-induced ROS generation in stem cell biology. Although the roles of ROS in metallic NP-related biological functions requires further investigation, modulation and characterization of metallic NP-induced ROS production are promising in the application of metallic NPs in the areas of regenerative medicine and medical devices. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Silver Nanoparticles: Synthesis, Characterization, Properties, Applications, and Therapeutic Approaches

by Xi-Feng Zhang, Zhi-Guo Liu, Wei Shen and Sangiliyandi Gurunathan

Int. J. Mol. Sci. 2016, 17(9), 1534; https://doi.org/10.3390/ijms17091534 - 13 Sep 2016

Cited by 2267 | Viewed by 84568

Abstract

Recent advances in nanoscience and nanotechnology radically changed the way we diagnose, treat, and prevent various diseases in all aspects of human life. Silver nanoparticles (AgNPs) are one of the most vital and fascinating nanomaterials among several metallic nanoparticles that are involved in [...] Read more.

Recent advances in nanoscience and nanotechnology radically changed the way we diagnose, treat, and prevent various diseases in all aspects of human life. Silver nanoparticles (AgNPs) are one of the most vital and fascinating nanomaterials among several metallic nanoparticles that are involved in biomedical applications. AgNPs play an important role in nanoscience and nanotechnology, particularly in nanomedicine. Although several noble metals have been used for various purposes, AgNPs have been focused on potential applications in cancer diagnosis and therapy. In this review, we discuss the synthesis of AgNPs using physical, chemical, and biological methods. We also discuss the properties of AgNPs and methods for their characterization. More importantly, we extensively discuss the multifunctional bio-applications of AgNPs; for example, as antibacterial, antifungal, antiviral, anti-inflammatory, anti-angiogenic, and anti-cancer agents, and the mechanism of the anti-cancer activity of AgNPs. In addition, we discuss therapeutic approaches and challenges for cancer therapy using AgNPs. Finally, we conclude by discussing the future perspective of AgNPs. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Silk Fibroin-Based Nanoparticles for Drug Delivery

by Zheng Zhao, Yi Li and Mao-Bin Xie

Int. J. Mol. Sci. 2015, 16(3), 4880-4903; https://doi.org/10.3390/ijms16034880 - 4 Mar 2015

Cited by 256 | Viewed by 19140

Abstract

Silk fibroin (SF) is a protein-based biomacromolecule with excellent biocompatibility, biodegradability and low immunogenicity. The development of SF-based nanoparticles for drug delivery have received considerable attention due to high binding capacity for various drugs, controlled drug release properties and mild preparation conditions. By [...] Read more.

Silk fibroin (SF) is a protein-based biomacromolecule with excellent biocompatibility, biodegradability and low immunogenicity. The development of SF-based nanoparticles for drug delivery have received considerable attention due to high binding capacity for various drugs, controlled drug release properties and mild preparation conditions. By adjusting the particle size, the chemical structure and properties, the modified or recombinant SF-based nanoparticles can be designed to improve the therapeutic efficiency of drugs encapsulated into these nanoparticles. Therefore, they can be used to deliver small molecule drugs (e.g., anti-cancer drugs), protein and growth factor drugs, gene drugs, etc. This paper reviews recent progress on SF-based nanoparticles, including chemical structure, properties, and preparation methods. In addition, the applications of SF-based nanoparticles as carriers for therapeutic drugs are also reviewed. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Mechanisms and Implications of Dual-Acting Methotrexate in Folate-Targeted Nanotherapeutic Delivery

by Pamela T. Wong and Seok Ki Choi

Int. J. Mol. Sci. 2015, 16(1), 1772-1790; https://doi.org/10.3390/ijms16011772 - 13 Jan 2015

Cited by 74 | Viewed by 12323

Abstract

The rational design of a nanoplatform in drug delivery plays a crucial role in determining its targeting specificity and efficacy in vivo. A conventional approach relies on the surface conjugation of a nanometer-sized particle with two functionally distinct types of molecules, one [...] Read more.

The rational design of a nanoplatform in drug delivery plays a crucial role in determining its targeting specificity and efficacy in vivo. A conventional approach relies on the surface conjugation of a nanometer-sized particle with two functionally distinct types of molecules, one as a targeting ligand, and the other as a therapeutic agent to be delivered to the diseased cell. However, an alternative simplified approach can be used, in which a single type of molecule displaying dual function as both a targeting ligand and therapeutic agent is conjugated to the nanoparticle. In this review, we evaluate the validity of this new strategy by using methotrexate, which displays multifunctional mechanisms of action. Methotrexate binds to the folate receptor, a surface biomarker frequently overexpressed in tumor cells, and also inhibits dihydrofolate reductase, an enzyme critical for cell survival and division. Thus we describe a series of fifth generation poly(amido amine) dendrimers conjugated with methotrexate, and discuss several lines of evidence supporting the efficacy of this new platform strategy based on surface plasmon resonance spectroscopy, enzyme activity assays, and cell-based studies with folate receptor (+) KB cancer cells. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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The Potential of Liposomes with Carbonic Anhydrase IX to Deliver Anticancer Ingredients to Cancer Cells in Vivo

by Huei Leng Helena Ng, Aiping Lu, Ge Lin, Ling Qin and Zhijun Yang

Int. J. Mol. Sci. 2015, 16(1), 230-255; https://doi.org/10.3390/ijms16010230 - 24 Dec 2014

Cited by 14 | Viewed by 9262

Abstract

Drug delivery nanocarriers, especially targeted drug delivery by liposomes are emerging as a class of therapeutics for cancer. Early research results suggest that liposomal therapeutics enhanced efficacy, while simultaneously reducing side effects, owing to properties such as more targeted localization in tumors and [...] Read more.

Drug delivery nanocarriers, especially targeted drug delivery by liposomes are emerging as a class of therapeutics for cancer. Early research results suggest that liposomal therapeutics enhanced efficacy, while simultaneously reducing side effects, owing to properties such as more targeted localization in tumors and active cellular uptake. Here, we highlight the features of immunoliposomes that distinguish them from previous anticancer therapies, and describe how these features provide the potential for therapeutic effects that are not achievable with other modalities. While a large number of studies has been published, the emphasis here is placed on the carbonic anhydrase IX (CA-IX) and the conjugated liposomes that are likely to open a new chapter on drug delivery system by using immunoliposomes to deliver anticancer ingredients to cancer cells in vivo. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Mechanistic Understanding of Toxicity from Nanocatalysts

by Cuijuan Jiang, Jianbo Jia and Shumei Zhai

Int. J. Mol. Sci. 2014, 15(8), 13967-13992; https://doi.org/10.3390/ijms150813967 - 12 Aug 2014

Cited by 25 | Viewed by 8628

Abstract

Nanoparticle-based catalysts, or nanocatalysts, have been applied in various industrial sectors, including refineries, petrochemical plants, the pharmaceutical industry, the chemical industry, food processing, and environmental remediation. As a result, there is an increasing risk of human exposure to nanocatalysts. This review evaluates the [...] Read more.

Nanoparticle-based catalysts, or nanocatalysts, have been applied in various industrial sectors, including refineries, petrochemical plants, the pharmaceutical industry, the chemical industry, food processing, and environmental remediation. As a result, there is an increasing risk of human exposure to nanocatalysts. This review evaluates the toxicity of popular nanocatalysts applied in industrial processes in cell and animal models. The molecular mechanisms associated with such nanotoxicity are emphasized to reveal common toxicity-inducing pathways from various nanocatalysts and the uniqueness of each specific nanocatalyst. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Biosurfactant Mediated Biosynthesis of Selected Metallic Nanoparticles

by Grażyna A. Płaza, Joanna Chojniak and Ibrahim M. Banat

Int. J. Mol. Sci. 2014, 15(8), 13720-13737; https://doi.org/10.3390/ijms150813720 - 8 Aug 2014

Cited by 95 | Viewed by 11199

Abstract

Developing a reliable experimental protocol for the synthesis of nanomaterials is one of the challenging topics in current nanotechnology particularly in the context of the recent drive to promote green technologies in their synthesis. The increasing need to develop clean, nontoxic and environmentally [...] Read more.

Developing a reliable experimental protocol for the synthesis of nanomaterials is one of the challenging topics in current nanotechnology particularly in the context of the recent drive to promote green technologies in their synthesis. The increasing need to develop clean, nontoxic and environmentally safe production processes for nanoparticles to reduce environmental impact, minimize waste and increase energy efficiency has become essential in this field. Consequently, recent studies on the use of microorganisms in the synthesis of selected nanoparticles are gaining increased interest as they represent an exciting area of research with considerable development potential. Microorganisms are known to be capable of synthesizing inorganic molecules that are deposited either intra- or extracellularly. This review presents a brief overview of current research on the use of biosurfactants in the biosynthesis of selected metallic nanoparticles and their potential importance. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Potential for Layered Double Hydroxides-Based, Innovative Drug Delivery Systems

by Kai Zhang, Zhi Ping Xu, Ji Lu, Zhi Yong Tang, Hui Jun Zhao, David A. Good and Ming Qian Wei

Int. J. Mol. Sci. 2014, 15(5), 7409-7428; https://doi.org/10.3390/ijms15057409 - 29 Apr 2014

Cited by 96 | Viewed by 11470

Abstract

Layered Double Hydroxides (LDHs)-based drug delivery systems have, for many years, shown great promises for the delivery of chemical therapeutics and bioactive molecules to mammalian cells in vitro and in vivo. This system offers high efficiency and drug loading density, as well as [...] Read more.

Layered Double Hydroxides (LDHs)-based drug delivery systems have, for many years, shown great promises for the delivery of chemical therapeutics and bioactive molecules to mammalian cells in vitro and in vivo. This system offers high efficiency and drug loading density, as well as excellent protection of loaded molecules from undesired degradation. Toxicological studies have also found LDHs to be biocompatible compared with other widely used nanoparticles, such as iron oxide, silica, and single-walled carbon nanotubes. A plethora of bio-molecules have been reported to either attach to the surface of or intercalate into LDH materials through co-precipitation or anion-exchange reaction, including amino acid and peptides, ATPs, vitamins, and even polysaccharides. Recently, LDHs have been used for gene delivery of small molecular nucleic acids, such as antisense, oligonucleotides, PCR fragments, siRNA molecules or sheared genomic DNA. These nano-medicines have been applied to target cells or organs in gene therapeutic approaches. This review summarizes current progress of the development of LDHs nanoparticle drug carriers for nucleotides, anti-inflammatory, anti-cancer drugs and recent LDH application in medical research. Ground breaking studies will be highlighted and an outlook of the possible future progress proposed. It is hoped that the layered inorganic material will open up new frontier of research, leading to new nano-drugs in clinical applications. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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Nanotoxicity Overview: Nano-Threat to Susceptible Populations

by Yang Li, Yi Zhang and Bing Yan

Int. J. Mol. Sci. 2014, 15(3), 3671-3697; https://doi.org/10.3390/ijms15033671 - 28 Feb 2014

Cited by 90 | Viewed by 11742

Abstract

Due to the increasing applications of nanomaterials and nanotechnology, potential danger of nanoparticle exposure has become a critical issue. However, recent nanotoxicity studies have mainly focused on the health risks to healthy adult population. The nanotoxicity effects on susceptible populations (such as pregnant, [...] Read more.

Due to the increasing applications of nanomaterials and nanotechnology, potential danger of nanoparticle exposure has become a critical issue. However, recent nanotoxicity studies have mainly focused on the health risks to healthy adult population. The nanotoxicity effects on susceptible populations (such as pregnant, neonate, diseased, and aged populations) have been overlooked. Due to the alterations in physiological structures and functions in susceptible populations, they often suffer more damage from the same exposure. Thus, it is urgent to understand the effects of nanoparticle exposure on these populations. In order to fill this gap, the potential effects of nanoparticles to pregnant females, neonate, diseased, and aged population, as well as the possible underlying mechanisms are reviewed in this article. Investigations show that responses from susceptible population to nanoparticle exposure are often more severe. Reduced protection mechanism, compromised immunity, and impaired self-repair ability in these susceptible populations may contribute to the aggravated toxicity effects. This review will help minimize adverse effects of nanoparticles to susceptible population in future nanotechnology applications. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2014)

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The Effects of Nanomaterials as Endocrine Disruptors

by Ivo Iavicoli, Luca Fontana, Veruscka Leso and Antonio Bergamaschi

Int. J. Mol. Sci. 2013, 14(8), 16732-16801; https://doi.org/10.3390/ijms140816732 - 14 Aug 2013

Cited by 181 | Viewed by 15726

Abstract

In recent years, nanoparticles have been increasingly used in several industrial, consumer and medical applications because of their unique physico-chemical properties. However, in vitro and in vivo studies have demonstrated that these properties are also closely associated with detrimental health effects. There is [...] Read more.

In recent years, nanoparticles have been increasingly used in several industrial, consumer and medical applications because of their unique physico-chemical properties. However, in vitro and in vivo studies have demonstrated that these properties are also closely associated with detrimental health effects. There is a serious lack of information on the potential nanoparticle hazard to human health, particularly on their possible toxic effects on the endocrine system. This topic is of primary importance since the disruption of endocrine functions is associated with severe adverse effects on human health. Consequently, in order to gather information on the hazardous effects of nanoparticles on endocrine organs, we reviewed the data available in the literature regarding the endocrine effects of in vitro and in vivo exposure to different types of nanoparticles. Our aim was to understand the potential endocrine disrupting risks posed by nanoparticles, to assess their underlying mechanisms of action and identify areas in which further investigation is needed in order to obtain a deeper understanding of the role of nanoparticles as endocrine disruptors. Current data support the notion that different types of nanoparticles are capable of altering the normal and physiological activity of the endocrine system. However, a critical evaluation of these findings suggests the need to interpret these results with caution since information on potential endocrine interactions and the toxicity of nanoparticles is quite limited. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2013)

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Effects of Nanotoxicity on Female Reproductivity and Fetal Development in Animal Models

by Jianling Sun, Qiu Zhang, Zhiping Wang and Bing Yan

Int. J. Mol. Sci. 2013, 14(5), 9319-9337; https://doi.org/10.3390/ijms14059319 - 29 Apr 2013

Cited by 87 | Viewed by 15363

Abstract

The extensive application of nanomaterials in industry, medicine and consumer products has raised concerns about their potential toxicity. The female population is particularly vulnerable and deserves special attention because toxicity in this group may impact both female reproductivity and fetal development. Mouse and [...] Read more.

The extensive application of nanomaterials in industry, medicine and consumer products has raised concerns about their potential toxicity. The female population is particularly vulnerable and deserves special attention because toxicity in this group may impact both female reproductivity and fetal development. Mouse and zebrafish models each have their own unique features and studies using these models to examine the potential toxicity of various nanoparticles are compared and summarized in this review. Several nanoparticles exhibit detrimental effects on female reproductivity as well as fetal development, and these adverse effects are related to nanoparticle composition, surface modification, dose, exposure route and animal species. Limited studies on the mechanisms of nanotoxicity are also documented and reviewed herein. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2013)

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Nanostructured Surfaces of Dental Implants

by Eriberto Bressan, Luca Sbricoli, Riccardo Guazzo, Ilaria Tocco, Marco Roman, Vincenzo Vindigni, Edoardo Stellini, Chiara Gardin, Letizia Ferroni, Stefano Sivolella and Barbara Zavan

Int. J. Mol. Sci. 2013, 14(1), 1918-1931; https://doi.org/10.3390/ijms14011918 - 17 Jan 2013

Cited by 57 | Viewed by 12445

Abstract

The structural and functional fusion of the surface of the dental implant with the surrounding bone (osseointegration) is crucial for the short and long term outcome of the device. In recent years, the enhancement of bone formation at the bone-implant interface has been [...] Read more.

The structural and functional fusion of the surface of the dental implant with the surrounding bone (osseointegration) is crucial for the short and long term outcome of the device. In recent years, the enhancement of bone formation at the bone-implant interface has been achieved through the modulation of osteoblasts adhesion and spreading, induced by structural modifications of the implant surface, particularly at the nanoscale level. In this context, traditional chemical and physical processes find new applications to achieve the best dental implant technology. This review provides an overview of the most common manufacture techniques and the related cells-surface interactions and modulation. A Medline and a hand search were conducted to identify studies concerning nanostructuration of implant surface and their related biological interaction. In this paper, we stressed the importance of the modifications on dental implant surfaces at the nanometric level. Nowadays, there is still little evidence of the long-term benefits of nanofeatures, as the promising results achieved in vitro and in animals have still to be confirmed in humans. However, the increasing interest in nanotechnology is undoubted and more research is going to be published in the coming years. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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Biopolymer-Based Nanoparticles for Drug/Gene Delivery and Tissue Engineering

by Sachiko Kaihara Nitta and Keiji Numata

Int. J. Mol. Sci. 2013, 14(1), 1629-1654; https://doi.org/10.3390/ijms14011629 - 14 Jan 2013

Cited by 565 | Viewed by 27216

Abstract

There has been a great interest in application of nanoparticles as biomaterials for delivery of therapeutic molecules such as drugs and genes, and for tissue engineering. In particular, biopolymers are suitable materials as nanoparticles for clinical application due to their versatile traits, including [...] Read more.

There has been a great interest in application of nanoparticles as biomaterials for delivery of therapeutic molecules such as drugs and genes, and for tissue engineering. In particular, biopolymers are suitable materials as nanoparticles for clinical application due to their versatile traits, including biocompatibility, biodegradability and low immunogenicity. Biopolymers are polymers that are produced from living organisms, which are classified in three groups: polysaccharides, proteins and nucleic acids. It is important to control particle size, charge, morphology of surface and release rate of loaded molecules to use biopolymer-based nanoparticles as drug/gene delivery carriers. To obtain a nano-carrier for therapeutic purposes, a variety of materials and preparation process has been attempted. This review focuses on fabrication of biocompatible nanoparticles consisting of biopolymers such as protein (silk, collagen, gelatin, β-casein, zein and albumin), protein-mimicked polypeptides and polysaccharides (chitosan, alginate, pullulan, starch and heparin). The effects of the nature of the materials and the fabrication process on the characteristics of the nanoparticles are described. In addition, their application as delivery carriers of therapeutic drugs and genes and biomaterials for tissue engineering are also reviewed. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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Intelligent Design of Nano-Scale Molecular Imaging Agents

by Sung Bae Kim, Mitsuru Hattori and Takeaki Ozawa

Int. J. Mol. Sci. 2012, 13(12), 16986-17005; https://doi.org/10.3390/ijms131216986 - 12 Dec 2012

Cited by 7 | Viewed by 8667

Abstract

Visual representation and quantification of biological processes at the cellular and subcellular levels within living subjects are gaining great interest in life science to address frontier issues in pathology and physiology. As intact living subjects do not emit any optical signature, visual representation [...] Read more.

Visual representation and quantification of biological processes at the cellular and subcellular levels within living subjects are gaining great interest in life science to address frontier issues in pathology and physiology. As intact living subjects do not emit any optical signature, visual representation usually exploits nano-scale imaging agents as the source of image contrast. Many imaging agents have been developed for this purpose, some of which exert nonspecific, passive, and physical interaction with a target. Current research interest in molecular imaging has mainly shifted to fabrication of smartly integrated, specific, and versatile agents that emit fluorescence or luminescence as an optical readout. These agents include luminescent quantum dots (QDs), biofunctional antibodies, and multifunctional nanoparticles. Furthermore, genetically encoded nano-imaging agents embedding fluorescent proteins or luciferases are now gaining popularity. These agents are generated by integrative design of the components, such as luciferase, flexible linker, and receptor to exert a specific on–off switching in the complex context of living subjects. In the present review, we provide an overview of the basic concepts, smart design, and practical contribution of recent nano-scale imaging agents, especially with respect to genetically encoded imaging agents. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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Vectors for Inhaled Gene Therapy in Lung Cancer. Application for Nano Oncology and Safety of Bio Nanotechnology

by Paul Zarogouldis, Nikos K. Karamanos, Konstantinos Porpodis, Kalliopi Domvri, Haidong Huang, Wolfgang Hohenforst-Schimdt, Eugene P. Goldberg and Konstantinos Zarogoulidis

Int. J. Mol. Sci. 2012, 13(9), 10828-10862; https://doi.org/10.3390/ijms130910828 - 29 Aug 2012

Cited by 41 | Viewed by 12580 | Correction

Abstract

Novel aerosol therapeutic modalities have been investigated for lung cancer. Inhaled gene therapy has presented safety and effectiveness previously in cystic fibrosis. However, safety concerns have been raised regarding the safety of non-viral vectors for inhaled gene therapy in lung cancer, and therefore [...] Read more.

Novel aerosol therapeutic modalities have been investigated for lung cancer. Inhaled gene therapy has presented safety and effectiveness previously in cystic fibrosis. However, safety concerns have been raised regarding the safety of non-viral vectors for inhaled gene therapy in lung cancer, and therefore small steps have been made towards this multifunctional treatment modality. During the last decade, numerous new nanocomplexes have been created and investigated as a safe gene delivery nano-vehicle. These formulations are multifunctional; they can be used as either local therapy or carrier for an effective inhaled gene therapy for lung cancer. Herein, we present current and future perspectives of nanocomplexes for inhaled gene therapy treatment in lung cancer. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2012)

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Antioxidant-Induced Stress

by Cleva Villanueva and Robert D. Kross

Int. J. Mol. Sci. 2012, 13(2), 2091-2109; https://doi.org/10.3390/ijms13022091 - 16 Feb 2012

Cited by 115 | Viewed by 12813

Abstract

Antioxidants are among the most popular health-protecting products, sold worldwide without prescription. Indeed, there are many reports showing the benefits of antioxidants but only a few questioning the possible harmful effects of these “drugs”. The normal balance between antioxidants and free radicals in [...] Read more.

Antioxidants are among the most popular health-protecting products, sold worldwide without prescription. Indeed, there are many reports showing the benefits of antioxidants but only a few questioning the possible harmful effects of these “drugs”. The normal balance between antioxidants and free radicals in the body is offset when either of these forces prevails. The available evidence on the harmful effects of antioxidants is analyzed in this review. In summary, a hypothesis is presented that “antioxidant-induced stress” results when antioxidants overwhelm the body’s free radicals. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles (special issue))

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Enabling Anticancer Therapeutics by Nanoparticle Carriers: The Delivery of Paclitaxel

by Yongjin Liu, Bin Zhang and Bing Yan

Int. J. Mol. Sci. 2011, 12(7), 4395-4413; https://doi.org/10.3390/ijms12074395 - 7 Jul 2011

Cited by 64 | Viewed by 11997

Abstract

Anticancer drugs, such as paclitaxel (PTX), are indispensable for the treatment of a variety of malignancies. However, the application of most drugs is greatly limited by the low water solubility, poor permeability, or high efflux from cells. Nanoparticles have been widely investigated to [...] Read more.

Anticancer drugs, such as paclitaxel (PTX), are indispensable for the treatment of a variety of malignancies. However, the application of most drugs is greatly limited by the low water solubility, poor permeability, or high efflux from cells. Nanoparticles have been widely investigated to enable drug delivery due to their low toxicity, sustained drug release, molecular targeting, and additional therapeutic and imaging functions. This review takes paclitaxel as an example and compares different nanoparticle-based delivery systems for their effectiveness in cancer chemotherapy. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles (special issue))

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Inorganic-Organic Hybrid Nanomaterials for Therapeutic and Diagnostic Imaging Applications

by Juan L. Vivero-Escoto and Yu-Tzu Huang

Int. J. Mol. Sci. 2011, 12(6), 3888-3927; https://doi.org/10.3390/ijms12063888 - 10 Jun 2011

Cited by 84 | Viewed by 12833

Abstract

Nanotechnology offers outstanding potential for future biomedical applications. In particular, due to their unique characteristics, hybrid nanomaterials have recently been investigated as promising platforms for imaging and therapeutic applications. This class of nanoparticles can not only retain valuable features of both inorganic and [...] Read more.

Nanotechnology offers outstanding potential for future biomedical applications. In particular, due to their unique characteristics, hybrid nanomaterials have recently been investigated as promising platforms for imaging and therapeutic applications. This class of nanoparticles can not only retain valuable features of both inorganic and organic moieties, but also provides the ability to systematically modify the properties of the hybrid material through the combination of functional elements. Moreover, the conjugation of targeting moieties on the surface of these nanomaterials gives them specific targeted imaging and therapeutic properties. In this review, we summarize the recent reports in the synthesis of hybrid nanomaterials and their applications in biomedical areas. Their applications as imaging and therapeutic agents in vivo will be highlighted. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles (special issue))

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Application of Magnetic Nanoparticles to Gene Delivery

by Daisuke Kami, Shogo Takeda, Yoko Itakura, Satoshi Gojo, Masatoshi Watanabe and Masashi Toyoda

Int. J. Mol. Sci. 2011, 12(6), 3705-3722; https://doi.org/10.3390/ijms12063705 - 7 Jun 2011

Cited by 139 | Viewed by 16683

Abstract

Nanoparticle technology is being incorporated into many areas of molecular science and biomedicine. Because nanoparticles are small enough to enter almost all areas of the body, including the circulatory system and cells, they have been and continue to be exploited for basic biomedical [...] Read more.

Nanoparticle technology is being incorporated into many areas of molecular science and biomedicine. Because nanoparticles are small enough to enter almost all areas of the body, including the circulatory system and cells, they have been and continue to be exploited for basic biomedical research as well as clinical diagnostic and therapeutic applications. For example, nanoparticles hold great promise for enabling gene therapy to reach its full potential by facilitating targeted delivery of DNA into tissues and cells. Substantial progress has been made in binding DNA to nanoparticles and controlling the behavior of these complexes. In this article, we review research on binding DNAs to nanoparticles as well as our latest study on non-viral gene delivery using polyethylenimine-coated magnetic nanoparticles. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles (special issue))

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Nanomedicine: Application Areas and Development Prospects

by Houria Boulaiz, Pablo J. Alvarez, Alberto Ramirez, Juan A. Marchal, Jose Prados, Fernando Rodríguez-Serrano, Macarena Perán, Consolación Melguizo and Antonia Aranega

Int. J. Mol. Sci. 2011, 12(5), 3303-3321; https://doi.org/10.3390/ijms12053303 - 19 May 2011

Cited by 137 | Viewed by 19161

Abstract

Nanotechnology, along with related concepts such as nanomaterials, nanostructures and nanoparticles, has become a priority area for scientific research and technological development. Nanotechnology, i.e., the creation and utilization of materials and devices at nanometer scale, already has multiple applications in electronics and [...] Read more.

Nanotechnology, along with related concepts such as nanomaterials, nanostructures and nanoparticles, has become a priority area for scientific research and technological development. Nanotechnology, i.e., the creation and utilization of materials and devices at nanometer scale, already has multiple applications in electronics and other fields. However, the greatest expectations are for its application in biotechnology and health, with the direct impact these could have on the quality of health in future societies. The emerging discipline of nanomedicine brings nanotechnology and medicine together in order to develop novel therapies and improve existing treatments. In nanomedicine, atoms and molecules are manipulated to produce nanostructures of the same size as biomolecules for interaction with human cells. This procedure offers a range of new solutions for diagnoses and “smart” treatments by stimulating the body’s own repair mechanisms. It will enhance the early diagnosis and treatment of diseases such as cancer, diabetes, Alzheimer’s, Parkinson’s and cardiovascular diseases. Preventive medicine may then become a reality. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles (special issue))

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Open AccessReview

Regulation of Enzyme Activity through Interactions with Nanoparticles

by Zhaochun Wu, Bin Zhang and Bing Yan

Int. J. Mol. Sci. 2009, 10(10), 4198-4209; https://doi.org/10.3390/ijms10104198 - 28 Sep 2009

Cited by 115 | Viewed by 16829

Abstract

The structure and function of an enzyme can be altered by nanoparticles (NPs). The interaction between enzyme and NPs is governed by the key properties of NPs, such as structure, size, surface chemistry, charge and surface shape. Recent representative studies on the NP-enzyme [...] Read more.

The structure and function of an enzyme can be altered by nanoparticles (NPs). The interaction between enzyme and NPs is governed by the key properties of NPs, such as structure, size, surface chemistry, charge and surface shape. Recent representative studies on the NP-enzyme interactions and the regulation of enzyme activity by NPs with different size, composition and surface modification are reviewed. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles (special issue))

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3 pages, 3038 KiB

Open AccessCorrection

Correction: Hung et al. Anti-Inflammatory Fibronectin-AgNP for Regulation of Biological Performance and Endothelial Differentiation Ability of Mesenchymal Stem Cells. Int. J. Mol. Sci. 2021, 22, 9262

by Huey-Shan Hung, Kai-Bo Chang, Cheng-Ming Tang, Tian-Ren Ku, Mei-Lang Kung, Alex Yang-Hao Yu, Chiung-Chyi Shen, Yi-Chin Yang, Hsien-Hsu Hsieh and Shan-hui Hsu

Int. J. Mol. Sci. 2022, 23(23), 14998; https://doi.org/10.3390/ijms232314998 - 30 Nov 2022

Cited by 1 | Viewed by 1090

Abstract

The authors wish to make the following correction to this paper [...] Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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