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Hepatocellular-Targeted mRNA Delivery Using Functionalized Selenium Nanoparticles In Vitro

Selenium’s (Se) chemopreventative and therapeutic properties have attracted attention in nanomedicine. Se nanoparticles (SeNPs) retain these properties of Se while possessing lower toxicity and higher bioavailability, potentiating their use in gene delivery. This study aimed to formulate SeNPs for e...

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Autores principales: Singh, Dhireshan, Singh, Moganavelli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025905/
https://www.ncbi.nlm.nih.gov/pubmed/33668320
http://dx.doi.org/10.3390/pharmaceutics13030298
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author Singh, Dhireshan
Singh, Moganavelli
author_facet Singh, Dhireshan
Singh, Moganavelli
author_sort Singh, Dhireshan
collection PubMed
description Selenium’s (Se) chemopreventative and therapeutic properties have attracted attention in nanomedicine. Se nanoparticles (SeNPs) retain these properties of Se while possessing lower toxicity and higher bioavailability, potentiating their use in gene delivery. This study aimed to formulate SeNPs for efficient binding and targeted delivery of FLuc-mRNA to hepatocellular carcinoma cells (HepG2) in vitro. The colorectal adenocarcinoma (Caco-2) and normal human embryonic kidney (HEK293) cells that do not have the asialoorosomucoid receptor (ASGPR) were utilized for comparison. SeNPs were functionalized with chitosan (CS), polyethylene glycol (PEG), and lactobionic acid (LA) for ASGPR targeting on HepG2 cells. Nanoparticles (NPs) and their mRNA-nanocomplexes were characterized by Fourier transform infra-red (FTIR) and UV-vis spectroscopy, transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Gel and fluorescence-based assays assessed the NP’s ability to bind and protect FLuc-mRNA. Cytotoxicity was determined using the -(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, while transgene expression was evaluated using the luciferase reporter gene assay. All NPs appeared spherical with sizes ranging 57.2–130.0 nm and zeta potentials 14.9–31.4 mV. NPs bound, compacted, and protected the mRNA from nuclease digestion and showed negligible cytotoxicity in vitro. Targeted gene expression was highest in the HepG2 cells using the LA targeted NPs. These NPs portend to be efficient nanocarriers of nucleic acids and warrant further investigation.
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spelling pubmed-80259052021-04-08 Hepatocellular-Targeted mRNA Delivery Using Functionalized Selenium Nanoparticles In Vitro Singh, Dhireshan Singh, Moganavelli Pharmaceutics Article Selenium’s (Se) chemopreventative and therapeutic properties have attracted attention in nanomedicine. Se nanoparticles (SeNPs) retain these properties of Se while possessing lower toxicity and higher bioavailability, potentiating their use in gene delivery. This study aimed to formulate SeNPs for efficient binding and targeted delivery of FLuc-mRNA to hepatocellular carcinoma cells (HepG2) in vitro. The colorectal adenocarcinoma (Caco-2) and normal human embryonic kidney (HEK293) cells that do not have the asialoorosomucoid receptor (ASGPR) were utilized for comparison. SeNPs were functionalized with chitosan (CS), polyethylene glycol (PEG), and lactobionic acid (LA) for ASGPR targeting on HepG2 cells. Nanoparticles (NPs) and their mRNA-nanocomplexes were characterized by Fourier transform infra-red (FTIR) and UV-vis spectroscopy, transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Gel and fluorescence-based assays assessed the NP’s ability to bind and protect FLuc-mRNA. Cytotoxicity was determined using the -(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, while transgene expression was evaluated using the luciferase reporter gene assay. All NPs appeared spherical with sizes ranging 57.2–130.0 nm and zeta potentials 14.9–31.4 mV. NPs bound, compacted, and protected the mRNA from nuclease digestion and showed negligible cytotoxicity in vitro. Targeted gene expression was highest in the HepG2 cells using the LA targeted NPs. These NPs portend to be efficient nanocarriers of nucleic acids and warrant further investigation. MDPI 2021-02-24 /pmc/articles/PMC8025905/ /pubmed/33668320 http://dx.doi.org/10.3390/pharmaceutics13030298 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Singh, Dhireshan
Singh, Moganavelli
Hepatocellular-Targeted mRNA Delivery Using Functionalized Selenium Nanoparticles In Vitro
title Hepatocellular-Targeted mRNA Delivery Using Functionalized Selenium Nanoparticles In Vitro
title_full Hepatocellular-Targeted mRNA Delivery Using Functionalized Selenium Nanoparticles In Vitro
title_fullStr Hepatocellular-Targeted mRNA Delivery Using Functionalized Selenium Nanoparticles In Vitro
title_full_unstemmed Hepatocellular-Targeted mRNA Delivery Using Functionalized Selenium Nanoparticles In Vitro
title_short Hepatocellular-Targeted mRNA Delivery Using Functionalized Selenium Nanoparticles In Vitro
title_sort hepatocellular-targeted mrna delivery using functionalized selenium nanoparticles in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025905/
https://www.ncbi.nlm.nih.gov/pubmed/33668320
http://dx.doi.org/10.3390/pharmaceutics13030298
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