International Journal of Molecular Sciences

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25 pages, 4676 KiB

Open AccessArticle

In Vitro Superparamagnetic Hyperthermia Employing Magnetite Gamma-Cyclodextrin Nanobioconjugates for Human Squamous Skin Carcinoma Therapy

by Isabela-Simona Caizer-Gaitan, Claudia-Geanina Watz, Costica Caizer, Cristina-Adriana Dehelean, Tiberiu Bratu, Zorin Crainiceanu, Adina Coroaba, Mariana Pinteala and Codruta-Marinela Soica

Int. J. Mol. Sci. 2024, 25(15), 8380; https://doi.org/10.3390/ijms25158380 - 31 Jul 2024

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Abstract

In vitro alternative therapy of human epidermoid squamous carcinoma (A431) by superparamagnetic hyperthermia (SPMHT) using Fe₃O₄ (magnetite) superparamagnetic nanoparticles (SPIONs) with an average diameter of 15.8 nm, bioconjugated with hydroxypropyl gamma-cyclodextrins (HP-γ-CDs) by means of polyacrylic acid (PAA) biopolymer, is [...] Read more.

In vitro alternative therapy of human epidermoid squamous carcinoma (A431) by superparamagnetic hyperthermia (SPMHT) using Fe₃O₄ (magnetite) superparamagnetic nanoparticles (SPIONs) with an average diameter of 15.8 nm, bioconjugated with hydroxypropyl gamma-cyclodextrins (HP-γ-CDs) by means of polyacrylic acid (PAA) biopolymer, is presented in this paper. The therapy was carried out at a temperature of 43 °C for 30 min using the concentrations of Fe₃O₄ ferrimagnetic nanoparticles from nanobioconjugates of 1, 5, and 10 mg/mL nanoparticles in cell suspension, which were previously found by us to be non-toxic for healthy cells (cell viabilities close to 100%), according to ISO standards (cell viability must be greater than 70%). The temperature for the in vitro therapy was obtained by the safe application (without exceeding the biological limit and cellular damage) of an alternating magnetic field with a frequency of 312.4 kHz and amplitudes of 168, 208, and 370 G, depending on the concentration of the magnetic nanoparticles. The optimal concentration of magnetic nanoparticles in suspension was found experimentally. The results obtained after the treatment show its high effectiveness in destroying the A431 tumor cells, up to 83%, with the possibility of increasing even more, which demonstrates the viability of the SPMHT method with Fe₃O₄-PAA–(HP-γ-CDs) nanobioconjugates for human squamous cancer therapy. Full article

(This article belongs to the Special Issue Nanoparticles in Nanobiotechnology and Nanomedicine)

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23 pages, 4066 KiB

Open AccessArticle

scL-2PAM: A Novel Countermeasure That Ameliorates Neuroinflammation and Neuronal Losses in Mice Exposed to an Anticholinesterase Organophosphate

by Manish Moghe, Sang-Soo Kim, Miaoyin Guan, Antonina Rait, Kathleen F. Pirollo, Joe B. Harford and Esther H. Chang

Int. J. Mol. Sci. 2024, 25(14), 7539; https://doi.org/10.3390/ijms25147539 - 9 Jul 2024

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Abstract

Due to their inhibition of acetylcholinesterase, organophosphates are among the most toxic of chemicals. Pralidoxime (a.k.a 2-PAM) is the only acetylcholinesterase reactivator approved in the U.S., but 2-PAM only poorly traverses the blood–brain barrier. Previously, we have demonstrated that scL-2PAM, a nanoformulation designed [...] Read more.

Due to their inhibition of acetylcholinesterase, organophosphates are among the most toxic of chemicals. Pralidoxime (a.k.a 2-PAM) is the only acetylcholinesterase reactivator approved in the U.S., but 2-PAM only poorly traverses the blood–brain barrier. Previously, we have demonstrated that scL-2PAM, a nanoformulation designed to enter the brain via receptor-mediated transcytosis, is superior to unencapsulated 2-PAM for reactivating brain acetylcholinesterase, ameliorating cholinergic crisis, and improving survival rates for paraoxon-exposed mice. Here, we employ histology and transcriptome analyses to assess the ability of scL-2PAM to prevent neurological sequelae including microglial activation, expression of inflammatory cytokines, and ultimately loss of neurons in mice surviving paraoxon exposures. Levels of the mRNA encoding chemokine ligand 2 (CCL2) were significantly upregulated after paraoxon exposures, with CCL2 mRNA levels in the brain correlating well with the intensity and duration of cholinergic symptoms. Our nanoformulation of 2-PAM was found to be superior to unencapsulated 2-PAM in reducing the levels of the CCL2 transcript. Moreover, brain histology revealed that scL-2PAM was more effective than unencapsulated 2-PAM in preventing microglial activation and the subsequent loss of neurons. Thus, scL-2PAM appears to be a new and improved countermeasure for reducing neuroinflammation and mitigating brain damage in survivors of organophosphate exposures. Full article

(This article belongs to the Special Issue Nanoparticles in Nanobiotechnology and Nanomedicine)

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16 pages, 2371 KiB

Open AccessArticle

An Efficient Method for Vault Nanoparticle Conjugation with Finely Adjustable Amounts of Antibodies and Small Molecules

by Giulia Tomaino, Camilla Pantaleoni, Annalisa D’Urzo, Carlo Santambrogio, Filippo Testa, Matilde Ciprandi, Davide Cotugno, Gianni Frascotti, Marco Vanoni and Paolo Tortora

Int. J. Mol. Sci. 2024, 25(12), 6629; https://doi.org/10.3390/ijms25126629 - 16 Jun 2024

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Abstract

Vaults are eukaryotic ribonucleoproteins consisting of 78 copies of the major vault protein (MVP), which assemble into a nanoparticle with an about 60 nm volume-based size, enclosing other proteins and RNAs. Regardless of their physiological role(s), vaults represent ideal, natural hollow nanoparticles, which [...] Read more.

Vaults are eukaryotic ribonucleoproteins consisting of 78 copies of the major vault protein (MVP), which assemble into a nanoparticle with an about 60 nm volume-based size, enclosing other proteins and RNAs. Regardless of their physiological role(s), vaults represent ideal, natural hollow nanoparticles, which are produced by the assembly of the sole MVP. Here, we have expressed in Komagataella phaffi and purified an MVP variant carrying a C-terminal Z peptide (vault-Z), which can tightly bind an antibody’s Fc portion, in view of targeted delivery. Via surface plasmon resonance analysis, we could determine a 2.5 nM affinity to the monoclonal antibody Trastuzumab (Tz)/vault-Z 1:1 interaction. Then, we characterized the in-solution interaction via co-incubation, ultracentrifugation, and analysis of the pelleted proteins. This showed virtually irreversible binding up to an at least 10:1 Tz/vault-Z ratio. As a proof of concept, we labeled the Fc portion of Tz with a fluorophore and conjugated it with the nanoparticle, along with either Tz or Cetuximab, another monoclonal antibody. Thus, we could demonstrate antibody-dependent, selective uptake by the SKBR3 and MDA-MB 231 breast cancer cell lines. These investigations provide a novel, flexible technological platform that significantly extends vault-Z’s applications, in that it can be stably conjugated with finely adjusted amounts of antibodies as well as of other molecules, such as fluorophores, cell-targeting peptides, or drugs, using the Fc portion as a scaffold. Full article

(This article belongs to the Special Issue Nanoparticles in Nanobiotechnology and Nanomedicine)

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20 pages, 2932 KiB

Open AccessArticle

Fullerene C₆₀ Conjugate with Folic Acid and Polyvinylpyrrolidone for Targeted Delivery to Tumor Cells

by Alina A. Borisenkova, Olga I. Bolshakova, Anna V. Titova, Irina S. Ryabokon, Maria A. Markova, Zhanna B. Lyutova, Victor P. Sedov, Elena Yu. Varfolomeeva, Vadim V. Bakhmetyev, Alexandr V. Arutyunyan, Vladimir S. Burdakov and Svetlana V. Sarantseva

Int. J. Mol. Sci. 2024, 25(10), 5350; https://doi.org/10.3390/ijms25105350 - 14 May 2024

Cited by 1 | Viewed by 1167

Abstract

The use of targeted drug delivery systems, including those based on selective absorption by certain receptors on the surface of the target cell, can lead to a decrease in the minimum effective dose and the accompanying toxicity of the drug, as well as [...] Read more.

The use of targeted drug delivery systems, including those based on selective absorption by certain receptors on the surface of the target cell, can lead to a decrease in the minimum effective dose and the accompanying toxicity of the drug, as well as an increase in therapeutic efficacy. A fullerene C₆₀ conjugate (FA-PVP-C₆₀) with polyvinylpyrrolidone (PVP) as a biocompatible spacer and folic acid (FA) as a targeting ligand for tumor cells with increased expression of folate receptors (FR) was obtained. Using ¹³C NMR spectroscopy, FT-IR, UV-Vis spectrometry, fluorometry and thermal analysis, the formation of the conjugate was confirmed and the nature of the binding of its components was established. The average particle sizes of the conjugate in aqueous solutions and cell culture medium were determined using dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). The FA-PVP-C₆₀ showed antiradical activity against ^•DPPH, ^•OH and O₂^•−, but at the same time, it was shown to generate ¹O₂. It was found that the conjugate in the studied concentration range (up to 200 μg/mL) is non-toxic in vitro and does not affect the cell cycle. To confirm the ability of the conjugate to selectively accumulate through folate-mediated endocytosis, its uptake into cells was analyzed by flow cytometry and confocal microscopy. It was shown that the conjugate is less absorbed by A549 cells with low FR expression than by HeLa, which has a high level of expression of this receptor. Full article

(This article belongs to the Special Issue Nanoparticles in Nanobiotechnology and Nanomedicine)

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39 pages, 21493 KiB

Open AccessArticle

Infection-Free and Enhanced Wound Healing Potential of Alginate Gels Incorporating Silver and Tannylated Calcium Peroxide Nanoparticles

by Alexandra Catalina Bîrcă, Oana Gherasim, Adelina-Gabriela Niculescu, Alexandru Mihai Grumezescu, Bogdan Ștefan Vasile, Dan Eduard Mihaiescu, Ionela Andreea Neacșu, Ecaterina Andronescu, Roxana Trușcă, Alina Maria Holban, Ariana Hudiță and George-Alexandru Croitoru

Int. J. Mol. Sci. 2024, 25(10), 5196; https://doi.org/10.3390/ijms25105196 - 10 May 2024

Cited by 1 | Viewed by 973

Abstract

The treatment of chronic wounds involves precise requirements and complex challenges, as the healing process cannot go beyond the inflammatory phase, therefore increasing the healing time and implying a higher risk of opportunistic infection. Following a better understanding of the healing process, oxygen [...] Read more.

The treatment of chronic wounds involves precise requirements and complex challenges, as the healing process cannot go beyond the inflammatory phase, therefore increasing the healing time and implying a higher risk of opportunistic infection. Following a better understanding of the healing process, oxygen supply has been validated as a therapeutic approach to improve and speed up wound healing. Moreover, the local implications of antimicrobial agents (such as silver-based nano-compounds) significantly support the normal healing process, by combating bacterial contamination and colonization. In this study, silver (S) and tannylated calcium peroxide (CaO₂@TA) nanoparticles were obtained by adapted microfluidic and precipitation synthesis methods, respectively. After complementary physicochemical evaluation, both types of nanoparticles were loaded in (Alg) alginate-based gels that were further evaluated as possible dressings for wound healing. The obtained composites showed a porous structure and uniform distribution of nanoparticles through the polymeric matrix (evidenced by spectrophotometric analysis and electron microscopy studies), together with a good swelling capacity. The as-proposed gel dressings exhibited a constant and suitable concentration of released oxygen, as shown for up to eight hours (UV–Vis investigation). The biofilm modulation data indicated a synergistic antimicrobial effect between silver and tannylated calcium peroxide nanoparticles, with a prominent inhibitory action against the Gram-positive bacterial biofilm after 48 h. Beneficial effects in the human keratinocytes cultured in contact with the obtained materials were demonstrated by the performed tests, such as MTT, LDH, and NO. Full article

(This article belongs to the Special Issue Nanoparticles in Nanobiotechnology and Nanomedicine)

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23 pages, 12320 KiB

Open AccessArticle

Harvesting the Power of Green Synthesis: Gold Nanoparticles Tailored for Prostate Cancer Therapy

by Marco Oliveira, André Sousa, Sara Sá, Sílvia Soares, Ana Cláudia Pereira, Ana Catarina Rocha, Patrick Pais, Diogo Ferreira, Cátia Almeida, Carla Luís, Cláudio Lima, Fábio Almeida, Álvaro Gestoso, Miguel-Correa Duarte, Pedro Barata, Daniela Martins-Mendes, Pilar Baylina, Carla F. Pereira and Rúben Fernandes

Int. J. Mol. Sci. 2024, 25(4), 2277; https://doi.org/10.3390/ijms25042277 - 14 Feb 2024

Cited by 2 | Viewed by 1288

Abstract

Biosynthetic gold nanoparticles (bAuNPs) present a promising avenue for enhancing bio-compatibility and offering an economically and environmentally responsible alternative to traditional production methods, achieved through a reduction in the use of hazardous chemicals. While the potential of bAuNPs as anticancer agents has been [...] Read more.

Biosynthetic gold nanoparticles (bAuNPs) present a promising avenue for enhancing bio-compatibility and offering an economically and environmentally responsible alternative to traditional production methods, achieved through a reduction in the use of hazardous chemicals. While the potential of bAuNPs as anticancer agents has been explored, there is a limited body of research focusing on the crucial physicochemical conditions influencing bAuNP production. In this study, we aim to identify the optimal growth phase of Pseudomonas aeruginosa cultures that maximizes the redox potential and coordinates the formation of bAuNPs with increased efficiency. The investigation employs 2,6-dichlorophenolindophenol (DCIP) as a redox indicator. Simultaneously, we explore the impact of temperature, pH, and incubation duration on the biosynthesis of bAuNPs, with a specific emphasis on their potential application as antitumor agents. Characterization of the resulting bAuNPs is conducted using ATR-FT-IR, TEM, and UV-Vis spectroscopy. To gain insights into the anticancer potential of bAuNPs, an experimental model is employed, utilizing both non-neoplastic (HPEpiC) and neoplastic (PC3) epithelial cell lines. Notably, P. aeruginosa cultures at 9 h/OD600 = 1, combined with biosynthesis at pH 9.0 for 24 h at 58 °C, produce bAuNPs that exhibit smaller, more spherical, and less aggregated characteristics. Crucially, these nanoparticles demonstrate negligible effects on HPEpiC cells while significantly impacting PC3 cells, resulting in reduced viability, migration, and lower IL-6 levels. This research lays the groundwork for the development of more specialized, economical, and ecologically friendly treatment modalities. Full article

(This article belongs to the Special Issue Nanoparticles in Nanobiotechnology and Nanomedicine)

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10 pages, 2831 KiB

Open AccessCommunication

Visualizing the 4D Impact of Gold Nanoparticles on DNA

by Hosam Abdelhady, Fadilah Aleanizy, Fulwah Alqahtani, Abdullah Bukhari, Sahar Soliman, Samaresh Sau and Arun Iyer

Int. J. Mol. Sci. 2024, 25(1), 542; https://doi.org/10.3390/ijms25010542 - 30 Dec 2023

Cited by 1 | Viewed by 1150

Abstract

The genotoxicity of AuNPs has sparked a scientific debate, with one perspective attributing it to direct DNA damage and another to oxidative damage through reactive oxygen species (ROS) activation. This controversy poses challenges for the widespread use of AuNPs in biomedical applications. To [...] Read more.

The genotoxicity of AuNPs has sparked a scientific debate, with one perspective attributing it to direct DNA damage and another to oxidative damage through reactive oxygen species (ROS) activation. This controversy poses challenges for the widespread use of AuNPs in biomedical applications. To address this debate, we employed four-dimensional atomic force microscopy (4DAFM) to examine the ability of AuNPs to damage DNA in vitro in the absence of ROS. To further examine whether the size and chemical coupling of these AuNPs are properties that control their toxicity, we exposed individual DNA molecules to three different types of AuNPs: small (average diameter = 10 nm), large (average diameter = 22 nm), and large conjugated (average diameter = 39 nm) AuNPs. We found that all types of AuNPs caused rapid (within minutes) and direct damage to the DNA molecules without the involvement of ROS. This research holds significant promise for advancing nanomedicines in diverse areas like viral therapy (including COVID-19), cancer treatment, and biosensor development for detecting DNA damage or mutations by resolving the ongoing debate regarding the genotoxicity mechanism. Moreover, it actively contributes to the continuous endeavors aimed at fully harnessing the capabilities of AuNPs across diverse biomedical fields, promising transformative healthcare solutions. Full article

(This article belongs to the Special Issue Nanoparticles in Nanobiotechnology and Nanomedicine)

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20 pages, 6059 KiB

Open AccessArticle

Single-Stage Microfluidic Synthesis Route for BaGdF₅:Tb³⁺-Based Nanocomposite Materials: Synthesis, Characterization and Biodistribution

by Zaira Gadzhimagomedova, Ilia Pankin, Vladimir Polyakov, Darya Khodakova, Pavel Medvedev, Pavel Zelenikhin, Nail Shamsutdinov, Sergey Chapek, Anna Goncharova and Alexander Soldatov

Int. J. Mol. Sci. 2023, 24(24), 17159; https://doi.org/10.3390/ijms242417159 - 5 Dec 2023

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Abstract

Rare-earth-doped nanoscaled BaGdF₅ is known as an efficient contrasting agent for X-ray micro-CT and NMR as well as a promising candidate for X-ray photodynamic therapy, thereby opening an opportunity for theragnostic applications. Conventional synthesis of Ln-doped BaGdF₅ consider a long-lasting batch [...] Read more.

Rare-earth-doped nanoscaled BaGdF₅ is known as an efficient contrasting agent for X-ray micro-CT and NMR as well as a promising candidate for X-ray photodynamic therapy, thereby opening an opportunity for theragnostic applications. Conventional synthesis of Ln-doped BaGdF₅ consider a long-lasting batch procedure, while a conjugation with photosensitizer usually implies a separate stage requiring active mixing. To the best of our knowledge, in this work, we for the first time obtain BaGdF₅:Tb³⁺ nanophosphors in a microfluidic route at temperatures as low as 100 °C while decreasing the time of thermal treatment down to 6 min. The proposed synthesis route allows for the obtaining of single-phase and monodisperse BaGd_1−xF5:Tb_x³⁺ nanoparticles with an averaged particle size of ca. 7–9 nm and hydrodynamic radius around 22 nm, as estimated from TEM and DLS, respectively. In addition, X-ray-excited optical luminescence has been recorded in situ for the series of nanophosphors synthesis with varied flow rates of Tb³⁺ and Gd³⁺ stock solutions, thereby anticipating a possible application of microfluidics for screening a wide range of possible co-dopants and reaction conditions and its effect on the optical properties of the synthesized materials. Moreover, we demonstrated that BaGd_1−xF₅:Tb_x³⁺@RoseBengal conjugates might be obtained in a single-stage route by implementing an additional mixer at the synthesis outcome, namely, by mixing the resulting reaction mixture containing nanoparticles with an equivalent flow of photosensitizer aqueous solution. In vitro cytotoxicity test declares moderate toxicity effect on different cell lines, while the results of flow cytometry indirectly confirm cellular uptake. Finally, we report long-term biodistribution monitoring of the synthesized nanocomposites assessed by X-ray micro-CT in the in vivo experiments on balb/c mice, which depicts an unusual character of agents’ accumulation. Full article

(This article belongs to the Special Issue Nanoparticles in Nanobiotechnology and Nanomedicine)

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19 pages, 3757 KiB

Open AccessArticle

Effect of the Protein Corona Formation on Antibody Functionalized Liquid Lipid Nanocarriers

by Saúl A. Navarro-Marchal, Marina Martín-Contreras, David Castro-Santiago, Teresa del Castillo-Santaella, Pablo Graván, Ana Belén Jódar-Reyes, Juan Antonio Marchal and José Manuel Peula-García

Int. J. Mol. Sci. 2023, 24(23), 16759; https://doi.org/10.3390/ijms242316759 - 25 Nov 2023

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Abstract

The main aim of this study is to report basic knowledge on how a protein corona (PC) could affect or modify the way in which multifunctionalized nanoparticles interact with cells. With this purpose, we have firstly optimized the development of a target-specific nanocarrier [...] Read more.

The main aim of this study is to report basic knowledge on how a protein corona (PC) could affect or modify the way in which multifunctionalized nanoparticles interact with cells. With this purpose, we have firstly optimized the development of a target-specific nanocarrier by coupling a specific fluorescent antibody on the surface of functionalized lipid liquid nanocapsules (LLNCs). Thus, an anti-HER2-FITC antibody (αHER2) has been used, HER2 being a surface receptor that is overexpressed in several tumor cells. Subsequently, the in vitro formation of a PC has been developed using fetal bovine serum supplemented with human fibrinogen. Dynamic Light Scattering (DLS), Nanoparticle Tracking Analysis (NTA), Laser Doppler Electrophoresis (LDE), and Gel Chromatography techniques have been used to assure a complete physico-chemical characterization of the nano-complexes with (LLNCs-αHER2-PC) and without (LLNCs-αHER2) the surrounding PC. In addition, cellular assays were performed to study the cellular uptake and the specific cellular-nanocarrier interactions using the SKBR3 (high expression of HER2) breast cancer cell line and human dermal fibroblasts (HDFa) (healthy cell line without expression of HER2 receptors as control), showing that the SKBR3 cell line had a higher transport rate (50-fold) than HDFa at 60 min with LLNCs-αHER2. Moreover, the SKBR3 cell line incubated with LLNCs-αHER2-PC suffered a significant reduction (40%) in the uptake. These results suggest that the formation of a PC onto LLNCs does not prevent specific cell targeting, although it does have an important influence on cell uptake. Full article

(This article belongs to the Special Issue Nanoparticles in Nanobiotechnology and Nanomedicine)

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24 pages, 7844 KiB

Open AccessArticle

Influence of the Synthesis Scheme of Nanocrystalline Cerium Oxide and Its Concentration on the Biological Activity of Cells Providing Wound Regeneration

by Ekaterina V. Silina, Victor A. Stupin, Natalia E. Manturova, Olga S. Ivanova, Anton L. Popov, Elena A. Mysina, Elena B. Artyushkova, Alexey A. Kryukov, Svetlana A. Dodonova, Maria P. Kruglova, Alexey A. Tinkov, Anatoly V. Skalny and Vladimir K. Ivanov

Int. J. Mol. Sci. 2023, 24(19), 14501; https://doi.org/10.3390/ijms241914501 - 24 Sep 2023

Cited by 5 | Viewed by 1637

Abstract

In the ongoing search for practical uses of rare-earth metal nanoparticles, cerium dioxide nanoparticles (nanoceria) have received special attention. The purpose of this research was to study the biomedical effects of nanocrystalline forms of cerium oxide obtained by different synthesis schemes and to [...] Read more.

In the ongoing search for practical uses of rare-earth metal nanoparticles, cerium dioxide nanoparticles (nanoceria) have received special attention. The purpose of this research was to study the biomedical effects of nanocrystalline forms of cerium oxide obtained by different synthesis schemes and to evaluate the effect of different concentrations of nanoceria (from 10⁻² to 10⁻⁶ M) on cells involved in the regeneration of skin cell structures such as fibroblasts, mesenchymal stem cells, and keratinocytes. Two different methods of nanoceria preparation were investigated: (1) CeO-NPs-1 by precipitation from aqueous solutions of cerium (III) nitrate hexahydrate and citric acid and (2) CeO-NPs-2 by hydrolysis of ammonium hexanitratocerate (IV) under conditions of thermal autoclaving. According to the X-ray diffraction, transmission electron microscopy, and dynamic light scattering data, CeO₂-1 consists of individual particles of cerium dioxide (3–5 nm) and their aggregates with diameters of 60–130 nm. CeO₂-2 comprises small aggregates of 8–20 nm in diameter, which consist of particles of 2–3 nm in size. Cell cultures of human fibroblasts, human mesenchymal stem cells, and human keratinocytes were cocultured with different concentrations of nanoceria sols (10⁻², 10⁻³, 10⁻⁴, 10⁻⁵, and 10⁻⁶ mol/L). The metabolic activity of all cell types was investigated by MTT test after 48 and 72 h, whereas proliferative activity and cytotoxicity were determined by quantitative cell culture counting and live/dead test. A dependence of biological effects on the method of nanoceria preparation and concentration was revealed. Data were obtained with respect to the optimal concentration of sol to achieve the highest metabolic effect in the used cell cultures. Hypotheses about the mechanisms of the obtained effects and the structure of a fundamentally new medical device for accelerated healing of skin wounds were formulated. The method of nanoceria synthesis and concentration fundamentally and significantly change the biological activity of cell cultures of different types—from suppression to pronounced stimulation. The best biological activity of cell cultures was determined through cocultivation with sols of citrate nanoceria (CeO-NPs-1) at a concentration of 10⁻³–10⁻⁴ M. Full article

(This article belongs to the Special Issue Nanoparticles in Nanobiotechnology and Nanomedicine)

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15 pages, 2457 KiB

Open AccessArticle

CRIF1 siRNA-Encapsulated PLGA Nanoparticles Suppress Tumor Growth in MCF-7 Human Breast Cancer Cells

by Shuyu Piao, Ikjun Lee, Seonhee Kim, Hyewon Park, Harsha Nagar, Su-Jeong Choi, Giang-Huong Vu, Minsoo Kim, Eun-Ok Lee, Byeong-Hwa Jeon, Dong Woon Kim, Youngduk Seo and Cuk-Seong Kim

Int. J. Mol. Sci. 2023, 24(8), 7453; https://doi.org/10.3390/ijms24087453 - 18 Apr 2023

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Abstract

Mitochondrial oxidative phosphorylation (OXPHOS) system dysfunction in cancer cells has been exploited as a target for anti-cancer therapeutic intervention. The downregulation of CR6-interacting factor 1 (CRIF1), an essential mito-ribosomal factor, can impair mitochondrial function in various cell types. In this study, we investigated [...] Read more.

Mitochondrial oxidative phosphorylation (OXPHOS) system dysfunction in cancer cells has been exploited as a target for anti-cancer therapeutic intervention. The downregulation of CR6-interacting factor 1 (CRIF1), an essential mito-ribosomal factor, can impair mitochondrial function in various cell types. In this study, we investigated whether CRIF1 deficiency induced by siRNA and siRNA nanoparticles could suppress MCF-7 breast cancer growth and tumor development, respectively. Our results showed that CRIF1 silencing decreased the assembly of mitochondrial OXPHOS complexes I and II, which induced mitochondrial dysfunction, mitochondrial reactive oxygen species (ROS) production, mitochondrial membrane potential depolarization, and excessive mitochondrial fission. CRIF1 inhibition reduced p53-induced glycolysis and apoptosis regulator (TIGAR) expression, as well as NADPH synthesis, leading to additional increases in ROS production. The downregulation of CRIF1 suppressed cell proliferation and inhibited cell migration through the induction of G0/G1 phase cell cycle arrest in MCF-7 breast cancer cells. Similarly, the intratumoral injection of CRIF1 siRNA-encapsulated PLGA nanoparticles inhibited tumor growth, downregulated the assembly of mitochondrial OXPHOS complexes I and II, and induced the expression of cell cycle protein markers (p53, p21, and p16) in MCF-7 xenograft mice. Thus, the inhibition of mitochondrial OXPHOS protein synthesis through CRIF1 deletion destroyed mitochondrial function, leading to elevated ROS levels and inducing antitumor effects in MCF-7 cells. Full article

(This article belongs to the Special Issue Nanoparticles in Nanobiotechnology and Nanomedicine)

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71 pages, 4706 KiB

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Nanoformulations in Pharmaceutical and Biomedical Applications: Green Perspectives

by Sanja Petrovic, Bogdan Bita and Marcela-Elisabeta Barbinta-Patrascu

Int. J. Mol. Sci. 2024, 25(11), 5842; https://doi.org/10.3390/ijms25115842 - 27 May 2024

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Abstract

This study provides a brief discussion of the major nanopharmaceuticals formulations as well as the impact of nanotechnology on the future of pharmaceuticals. Effective and eco-friendly strategies of biofabrication are also highlighted. Modern approaches to designing pharmaceutical nanoformulations (e.g., 3D printing, Phyto-Nanotechnology, Biomimetics/Bioinspiration, [...] Read more.

This study provides a brief discussion of the major nanopharmaceuticals formulations as well as the impact of nanotechnology on the future of pharmaceuticals. Effective and eco-friendly strategies of biofabrication are also highlighted. Modern approaches to designing pharmaceutical nanoformulations (e.g., 3D printing, Phyto-Nanotechnology, Biomimetics/Bioinspiration, etc.) are outlined. This paper discusses the need to use natural resources for the “green” design of new nanoformulations with therapeutic efficiency. Nanopharmaceuticals research is still in its early stages, and the preparation of nanomaterials must be carefully considered. Therefore, safety and long-term effects of pharmaceutical nanoformulations must not be overlooked. The testing of nanopharmaceuticals represents an essential point in their further applications. Vegetal scaffolds obtained by decellularizing plant leaves represent a valuable, bioinspired model for nanopharmaceutical testing that avoids using animals. Nanoformulations are critical in various fields, especially in pharmacy, medicine, agriculture, and material science, due to their unique properties and advantages over conventional formulations that allows improved solubility, bioavailability, targeted drug delivery, controlled release, and reduced toxicity. Nanopharmaceuticals have transitioned from experimental stages to being a vital component of clinical practice, significantly improving outcomes in medical fields for cancer treatment, infectious diseases, neurological disorders, personalized medicine, and advanced diagnostics. Here are the key points highlighting their importance. The significant challenges, opportunities, and future directions are mentioned in the final section. Full article

(This article belongs to the Special Issue Nanoparticles in Nanobiotechnology and Nanomedicine)

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