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Therapeutic potential of functionalized siRNA nanoparticles on regression of liver cancer in experimental mice
Short interfering RNA (siRNA) possesses special ability of silencing specific gene. To increase siRNA stability, transportation and its uptake by tumor cells, effective delivery to the appropriate target cells is a major challenge of siRNA-based therapy. In the present study, an effective, safe and...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825139/ https://www.ncbi.nlm.nih.gov/pubmed/31676815 http://dx.doi.org/10.1038/s41598-019-52142-4 |
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author | Khan, Azmat Ali Alanazi, Amer M. Jabeen, Mumtaz Chauhan, Arun Ansari, Mohammad Azam |
author_facet | Khan, Azmat Ali Alanazi, Amer M. Jabeen, Mumtaz Chauhan, Arun Ansari, Mohammad Azam |
author_sort | Khan, Azmat Ali |
collection | PubMed |
description | Short interfering RNA (siRNA) possesses special ability of silencing specific gene. To increase siRNA stability, transportation and its uptake by tumor cells, effective delivery to the appropriate target cells is a major challenge of siRNA-based therapy. In the present study, an effective, safe and biocompatible survivin siRNA encapsulated, GalNAc decorated PEGylated PLGA nanoconjugates (NCs) viz., GalNAc@PEG@siRNA-PLGA were engineered and their synergistic antitumor efficacy was evaluated for targeted delivery in HCC bearing experimental mice. GalNAc@PEG@siRNA-PLGA NCs were characterized for size, bioavailability, toxicity and biocompatibility. Their antitumor potential was evaluated considering gene silencing, apoptosis, histopathology and survival of treated mice. Exceptional accumulation of hepatocytes, reduction in survivin expression and prominent regression in tumor size confirmed the ASGPR-mediated uptake of ligand-anchored NCs and silencing of survivin gene in a targeted manner. Increased DNA fragmentation and potential modulation of caspase-3, Bax and Bcl-2 factors specified the induction of apoptosis that helped in significant inhibition of HCC progression. The potential synchronous and tumor selective delivery of versatile NCs indicated the effective payloads towards the target site, increased apoptosis in cancer cells and improved survival of treated animals. |
format | Online Article Text |
id | pubmed-6825139 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68251392019-11-12 Therapeutic potential of functionalized siRNA nanoparticles on regression of liver cancer in experimental mice Khan, Azmat Ali Alanazi, Amer M. Jabeen, Mumtaz Chauhan, Arun Ansari, Mohammad Azam Sci Rep Article Short interfering RNA (siRNA) possesses special ability of silencing specific gene. To increase siRNA stability, transportation and its uptake by tumor cells, effective delivery to the appropriate target cells is a major challenge of siRNA-based therapy. In the present study, an effective, safe and biocompatible survivin siRNA encapsulated, GalNAc decorated PEGylated PLGA nanoconjugates (NCs) viz., GalNAc@PEG@siRNA-PLGA were engineered and their synergistic antitumor efficacy was evaluated for targeted delivery in HCC bearing experimental mice. GalNAc@PEG@siRNA-PLGA NCs were characterized for size, bioavailability, toxicity and biocompatibility. Their antitumor potential was evaluated considering gene silencing, apoptosis, histopathology and survival of treated mice. Exceptional accumulation of hepatocytes, reduction in survivin expression and prominent regression in tumor size confirmed the ASGPR-mediated uptake of ligand-anchored NCs and silencing of survivin gene in a targeted manner. Increased DNA fragmentation and potential modulation of caspase-3, Bax and Bcl-2 factors specified the induction of apoptosis that helped in significant inhibition of HCC progression. The potential synchronous and tumor selective delivery of versatile NCs indicated the effective payloads towards the target site, increased apoptosis in cancer cells and improved survival of treated animals. Nature Publishing Group UK 2019-11-01 /pmc/articles/PMC6825139/ /pubmed/31676815 http://dx.doi.org/10.1038/s41598-019-52142-4 Text en © The Author(s) 2019, corrected publication 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Khan, Azmat Ali Alanazi, Amer M. Jabeen, Mumtaz Chauhan, Arun Ansari, Mohammad Azam Therapeutic potential of functionalized siRNA nanoparticles on regression of liver cancer in experimental mice |
title | Therapeutic potential of functionalized siRNA nanoparticles on regression of liver cancer in experimental mice |
title_full | Therapeutic potential of functionalized siRNA nanoparticles on regression of liver cancer in experimental mice |
title_fullStr | Therapeutic potential of functionalized siRNA nanoparticles on regression of liver cancer in experimental mice |
title_full_unstemmed | Therapeutic potential of functionalized siRNA nanoparticles on regression of liver cancer in experimental mice |
title_short | Therapeutic potential of functionalized siRNA nanoparticles on regression of liver cancer in experimental mice |
title_sort | therapeutic potential of functionalized sirna nanoparticles on regression of liver cancer in experimental mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825139/ https://www.ncbi.nlm.nih.gov/pubmed/31676815 http://dx.doi.org/10.1038/s41598-019-52142-4 |
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