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Nanomaterials
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Anti-Cancer, Biochemical and Immunological Activity of Nanoparticles...
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Anti-Cancer, Biochemical and Immunological Activity of Nanoparticles

A special issue of Nanomaterials (ISSN 2079-4991). This special issue belongs to the section "Biology and Medicines".

Deadline for manuscript submissions: closed (15 February 2020) | Viewed by 16518

Special Issue Editor

Prof. Dr. Robert K. DeLong

E-Mail Website
Guest Editor
Director of mRNA Technologies, Landmark Bio, PPLC, 300 North Beacon Street, Watertown, MA, USA
Interests: nanoscale biomolecular interactions; delivery of therapeutic RNA and mRNA by nanoparticles; antiviral and anticancer activity of nanoparticles and composites

Special Issue Information

Dear Colleagues,

It is an exciting time for nanomaterials. Their biomedical applications are numerous, and as their drug, nucleic acid, and protein complexes and conjugates begin translating from cell culture to animal studies and into the clinic, this gives us new hope in the fight against many cancers and possibly diseases with bacterial or viral pathogenesis. Research is now very active on what the anticancer, biochemical, and immunological mechanisms are for nanoparticles. For example, some groups have reported that certain nanoparticle compositions can inhibit enzymes and reduce their biochemical activity, and this may have potential applications for new cancer therapeutic or antibacterial strategies. Others utilize various synthetic chemistries to produce nanoparticle core-shell structures and composites that may have tunable physico-chemical properties and biological activities. For cancer nanotechnology, an exciting area is combining nanoparticles with targeting  or therapeutic antibodies to better direct them to the tumor and/or elicit a desirable biochemical and immunological effect. This Special Issue seeks contributers from all branches of applied nanotechnology with a focus on anticancer, biochemical, and immunological activities as potential therapeutic or diagnostic agents.

Dr. Robert K. DeLong
Guest Editor

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Published Papers (4 papers)

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10 pages, 3299 KiB  
Article
Intercellular Trafficking of Gold Nanostars in Uveal Melanoma Cells for Plasmonic Photothermal Therapy
by Rubén Ahijado-Guzmán, Natalia Sánchez-Arribas, María Martínez-Negro, Guillermo González-Rubio, María Santiago-Varela, María Pardo, Antonio Piñeiro, Iván López-Montero, Elena Junquera and Andrés Guerrero-Martínez
Nanomaterials 2020, 10(3), 590; https://doi.org/10.3390/nano10030590 - 24 Mar 2020
Cited by 17 | Viewed by 3518
Abstract
Efficient plasmonic photothermal therapies (PPTTs) using non-harmful pulse laser irradiation at the near-infrared (NIR) are a highly sought goal in nanomedicine. These therapies rely on the use of plasmonic nanostructures to kill cancer cells while minimizing the applied laser power density. Cancer cells [...] Read more.
Efficient plasmonic photothermal therapies (PPTTs) using non-harmful pulse laser irradiation at the near-infrared (NIR) are a highly sought goal in nanomedicine. These therapies rely on the use of plasmonic nanostructures to kill cancer cells while minimizing the applied laser power density. Cancer cells have an unsettled capacity to uptake, retain, release, and re-uptake gold nanoparticles, thus offering enormous versatility for research. In this work, we have studied such cell capabilities for nanoparticle trafficking and its impact on the effect of photothermal treatments. As our model system, we chose uveal (eye) melanoma cells, since laser-assisted eye surgery is routinely used to treat glaucoma and cataracts, or vision correction in refractive surgery. As nanostructure, we selected gold nanostars (Au NSs) due to their high photothermal efficiency at the near-infrared (NIR) region of the electromagnetic spectrum. We first investigated the photothermal effect on the basis of the dilution of Au NSs induced by cell division. Using this approach, we obtained high PPTT efficiency after several cell division cycles at an initial low Au NS concentration (pM regime). Subsequently, we evaluated the photothermal effect on account of cell division upon mixing Au NS-loaded and non-loaded cells. Upon such mixing, we observed trafficking of Au NSs between loaded and non-loaded cells, thus achieving effective PPTT after several division cycles under low irradiation conditions (below the maximum permissible exposure threshold of skin). Our study reveals the ability of uveal melanoma cells to release and re-uptake Au NSs that maintain their plasmonic photothermal properties throughout several cell division cycles and re-uptake. This approach may be readily extrapolated to real tissue and even to treat in situ the eye tumor itself. We believe that our method can potentially be used as co-therapy to disperse plasmonic gold nanostructures across affected tissues, thus increasing the effectiveness of classic PPTT. Full article
(This article belongs to the Special Issue Anti-Cancer, Biochemical and Immunological Activity of Nanoparticles )
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14 pages, 4546 KiB  
Article
Fabrication of Supercritical Antisolvent (SAS) Process-Assisted Fisetin-Encapsulated Poly (Vinyl Pyrrolidone) (PVP) Nanocomposites for Improved Anticancer Therapy
by Lin-Fei Chen, Pei-Yao Xu, Chao-Ping Fu, Ranjith Kumar Kankala, Ai-Zheng Chen and Shi-Bin Wang
Nanomaterials 2020, 10(2), 322; https://doi.org/10.3390/nano10020322 - 13 Feb 2020
Cited by 28 | Viewed by 4115
Abstract
Due to its hydrophobicity, fisetin (FIS) often suffers from several limitations in terms of its applicability during the fabrication of pharmaceutical formulations. To overcome this intrinsic limitation of hydrophobicity, we demonstrate here the generation of poly (vinyl pyrrolidone) (PVP)-encapsulated FIS nanoparticles (FIS-PVP NPs) [...] Read more.
Due to its hydrophobicity, fisetin (FIS) often suffers from several limitations in terms of its applicability during the fabrication of pharmaceutical formulations. To overcome this intrinsic limitation of hydrophobicity, we demonstrate here the generation of poly (vinyl pyrrolidone) (PVP)-encapsulated FIS nanoparticles (FIS-PVP NPs) utilizing a supercritical antisolvent (SAS) method to enhance its aqueous solubility and substantial therapeutic effects. In this context, the effects of various processing and formulation parameters, including the solvent/antisolvent ratio, drug/polymer (FIS/PVP) mass ratio, and solution flow rate, on the eventual particle size as well as on distribution were investigated using a 23 factorial experimental design. Notably, the FIS/PVP mass ratio significantly affected the morphological attributes of the resultant particles. Initially, the designed constructs were characterized systematically using various techniques (e.g., chemical functionalities were examined with Fourier-transform infrared (FTIR) spectroscopy, and physical states were examined with X-ray diffraction analysis (XRD) and differential scanning calorimetry (DSC) techniques). In addition, drug release as well as cytotoxicity evaluations in vitro indicated that the nanosized polymer-coated particles showed augmented performance efficiency compared to the free drug, which was attributable to the improvement in the dissolution rate of the FIS-PVP NPs due to their small size, facilitating a higher surface area over the raw form of FIS. Our findings show that the designed SAS process-assisted nanoconstructs with augmented bioavailability, have great potential for applications in pharmaceutics. Full article
(This article belongs to the Special Issue Anti-Cancer, Biochemical and Immunological Activity of Nanoparticles )
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12 pages, 1597 KiB  
Article
Codelivery of Genistein and miRNA-29b to A549 Cells Using Aptamer-Hybrid Nanoparticle Bioconjugates
by Koita Sacko, Karthik Thangavel and Sunday A. Shoyele
Nanomaterials 2019, 9(7), 1052; https://doi.org/10.3390/nano9071052 - 23 Jul 2019
Cited by 37 | Viewed by 4675
Abstract
This study aimed to evaluate the anti-cancer effect of a combination therapy of miRNA-29b and genistein loaded in mucin-1 (MUC 1)-aptamer functionalized hybrid nanoparticles in non-small cell lung cancer (NSCLC) A549 cell line. Genistein-miRNA-29b-loaded hybrid nanoparticles (GMLHN) was prepared and characterized. Particle size [...] Read more.
This study aimed to evaluate the anti-cancer effect of a combination therapy of miRNA-29b and genistein loaded in mucin-1 (MUC 1)-aptamer functionalized hybrid nanoparticles in non-small cell lung cancer (NSCLC) A549 cell line. Genistein-miRNA-29b-loaded hybrid nanoparticles (GMLHN) was prepared and characterized. Particle size and zeta potential were measured using photon correlation spectroscopy (PCS). Encapsulation efficiency and loading efficiency were determined using HPLC. Preferential internalization of MUC 1-aptamer functionalized GMLHN by A549 cells was evaluated and compared to normal MRC-5 cells. The ability of GMLHN to downregulate targeted oncoproteins Phosphorylated protein kinase, strain AK, Thymoma (Phosphorylated protein kinase B) (pAKT), Phosphorylated phosphoinositide 3-kinase (p-PI3K), DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) and Myeloid Cell Leukemia Sequence 1 (MCL 1) was evaluated using western blot, while antiproliferative effect and ability to initiate apoptosis was also assessed in A549 cells. MUC 1-aptamer functionalized GMLHN nanoparticles were prepared. These nanoparticles were preferentially internalized by A549 cells but less so, in MRC-5 cells. pAKT, p-PI3K, DNMT3B and MCL 1 were efficiently downregulated by these nanoparticles without affecting the levels of AKT and PI3K in A549 cells. GMLHN demonstrated a superior antiproliferative effect compared to individual genistein and miRNA-29b-loaded nanoparticles. Results generated were able to demonstrate that genistein-miRNA-29b-loaded hybrid nanoparticles (GMLHN) could be a potential treatment modality for NSCLC because of the ability of the payloads to attack multiple targets. Full article
(This article belongs to the Special Issue Anti-Cancer, Biochemical and Immunological Activity of Nanoparticles )
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11 pages, 2013 KiB  
Brief Report
Comparative Molecular Immunological Activity of Physiological Metal Oxide Nanoparticle and its Anticancer Peptide and RNA Complexes
by Robert K. DeLong, Jeffrey Comer, Elza Neelima Mathew and Majid Jaberi-Douraki
Nanomaterials 2019, 9(12), 1670; https://doi.org/10.3390/nano9121670 - 22 Nov 2019
Cited by 13 | Viewed by 3514
Abstract
Currently, there is a great interest in nanoparticle-based vaccine delivery. Recent studies suggest that nanoparticles when introduced into the biological milieu are not simply passive carriers but may also contribute immunological activity themselves or of their own accord. For example there is considerable [...] Read more.
Currently, there is a great interest in nanoparticle-based vaccine delivery. Recent studies suggest that nanoparticles when introduced into the biological milieu are not simply passive carriers but may also contribute immunological activity themselves or of their own accord. For example there is considerable interest in the biomedical applications of one of the physiologically-based inorganic metal oxide nanoparticle, zinc oxide (ZnO). Indeed zinc oxide (ZnO) NP are now recognized as a nanoscale chemotherapeutic or anticancer nanoparticle (ANP) and several recent reports suggest ZnO NP and/or its complexes with drug and RNA induce a potent antitumor response in immuno-competent mouse models. A variety of cell culture studies have shown that ZnO NP can induce cytokines such as IFN-γ, TNF-α, IL-2, and IL-12 which are known to regulate the tumor microenvironment. Much less work has been done on magnesium oxide (MgO), cobalt oxide (Co3O4), or nickel oxide (NiO); however, despite the fact that these physiologically-based metal oxide NP are reported to functionally load and assemble RNA and protein onto their surface and may thus also be of potential interest as nanovaccine platform. Here we initially compared in vitro immunogenicity of ZnO and Co3O4 NP and their effects on cancer-associated or tolerogenic cytokines. Based on these data we moved ZnO NP forward to testing in the ex vivo splenocyte assay relative to MgO and NiO NP and these data showed significant difference for flow cytometry sorted population for ZnO-NP, relative to NiO and MgO. These data suggesting both molecular and cellular immunogenic activity, a double-stranded anticancer RNA (ACR), polyinosinic:poly cytidylic acid (poly I:C) known to bind ZnO NP; when ZnO-poly I:C was injected into B16F10-BALB/C tumor significantly induced, IL-2 and IL-12 as shown by Cohen’s d test. LL37 is an anticancer peptide (ACP) currently in clinical trials as an intratumoral immuno-therapeutic agent against metastatic melanoma. LL37 is known to bind poly I:C where it is thought to compete for receptor binding on the surface of some immune cells, metastatic melanoma and lung cells. Molecular dynamic simulations revealed association of LL37 onto ZnO NP confirmed by gel shift assay. Thus using the well-characterized model human lung cancer model cell line (BEAS-2B), poly I:C RNA, LL37 peptide, or LL37-poly I:C complexes were loaded onto ZnO NP and delivered to BEAS-2B lung cells, and the effect on the main cancer regulating cytokine, IL-6 determined by ELISA. Surprisingly ZnO-LL37, but not ZnO-poly I:C or the more novel tricomplex (ZnO-LL37-poly I:C) significantly suppressed IL-6 by >98–99%. These data support the further evaluation of physiological metal oxide compositions, so-called physiometacomposite (PMC) materials and their formulation with anticancer peptide (ACP) and/or anticancer RNA (ACR) as a potential new class of immuno-therapeutic against melanoma and potentially lung carcinoma or other cancers. Full article
(This article belongs to the Special Issue Anti-Cancer, Biochemical and Immunological Activity of Nanoparticles )
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