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Nanoparticle encapsulation of non-genotoxic p53 activator Inauhzin-C for improved therapeutic efficacy
The tumor suppressor protein p53 remains in a wild type but inactive form in ~50% of all human cancers. Thus, activating it becomes an attractive approach for targeted cancer therapies. In this regard, our lab has previously discovered a small molecule, Inauhzin (INZ), as a potent p53 activator with...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171090/ https://www.ncbi.nlm.nih.gov/pubmed/34093867 http://dx.doi.org/10.7150/thno.57404 |
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author | Bhattarai, Nimisha Wang, Jieqiong Nguyen, Daniel Yang, Xiaoxiao Helmers, Linh Paruch, Jennifer Li, Li Zhang, Yiwei Meng, Kun Wang, Alun Jayawickramarajah, Janarthanan Wang, Binghe Zeng, Shelya Lu, Hua |
author_facet | Bhattarai, Nimisha Wang, Jieqiong Nguyen, Daniel Yang, Xiaoxiao Helmers, Linh Paruch, Jennifer Li, Li Zhang, Yiwei Meng, Kun Wang, Alun Jayawickramarajah, Janarthanan Wang, Binghe Zeng, Shelya Lu, Hua |
author_sort | Bhattarai, Nimisha |
collection | PubMed |
description | The tumor suppressor protein p53 remains in a wild type but inactive form in ~50% of all human cancers. Thus, activating it becomes an attractive approach for targeted cancer therapies. In this regard, our lab has previously discovered a small molecule, Inauhzin (INZ), as a potent p53 activator with no genotoxicity. Method: To improve its efficacy and bioavailability, here we employed nanoparticle encapsulation, making INZ-C, an analog of INZ, to nanoparticle-encapsulated INZ-C (n-INZ-C). Results: This approach significantly improved p53 activation and inhibition of lung and colorectal cancer cell growth by n-INZ-C in vitro and in vivo while it displayed a minimal effect on normal human Wi38 and mouse MEF cells. The improved activity was further corroborated with the enhanced cellular uptake observed in cancer cells and minimal cellular uptake observed in normal cells. In vivo pharmacokinetic evaluation of these nanoparticles showed that the nanoparticle encapsulation prolongates the half-life of INZ-C from 2.5 h to 5 h in mice. Conclusions: These results demonstrate that we have established a nanoparticle system that could enhance the bioavailability and efficacy of INZ-C as a potential anti-cancer therapeutic. |
format | Online Article Text |
id | pubmed-8171090 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-81710902021-06-03 Nanoparticle encapsulation of non-genotoxic p53 activator Inauhzin-C for improved therapeutic efficacy Bhattarai, Nimisha Wang, Jieqiong Nguyen, Daniel Yang, Xiaoxiao Helmers, Linh Paruch, Jennifer Li, Li Zhang, Yiwei Meng, Kun Wang, Alun Jayawickramarajah, Janarthanan Wang, Binghe Zeng, Shelya Lu, Hua Theranostics Research Paper The tumor suppressor protein p53 remains in a wild type but inactive form in ~50% of all human cancers. Thus, activating it becomes an attractive approach for targeted cancer therapies. In this regard, our lab has previously discovered a small molecule, Inauhzin (INZ), as a potent p53 activator with no genotoxicity. Method: To improve its efficacy and bioavailability, here we employed nanoparticle encapsulation, making INZ-C, an analog of INZ, to nanoparticle-encapsulated INZ-C (n-INZ-C). Results: This approach significantly improved p53 activation and inhibition of lung and colorectal cancer cell growth by n-INZ-C in vitro and in vivo while it displayed a minimal effect on normal human Wi38 and mouse MEF cells. The improved activity was further corroborated with the enhanced cellular uptake observed in cancer cells and minimal cellular uptake observed in normal cells. In vivo pharmacokinetic evaluation of these nanoparticles showed that the nanoparticle encapsulation prolongates the half-life of INZ-C from 2.5 h to 5 h in mice. Conclusions: These results demonstrate that we have established a nanoparticle system that could enhance the bioavailability and efficacy of INZ-C as a potential anti-cancer therapeutic. Ivyspring International Publisher 2021-05-12 /pmc/articles/PMC8171090/ /pubmed/34093867 http://dx.doi.org/10.7150/thno.57404 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Bhattarai, Nimisha Wang, Jieqiong Nguyen, Daniel Yang, Xiaoxiao Helmers, Linh Paruch, Jennifer Li, Li Zhang, Yiwei Meng, Kun Wang, Alun Jayawickramarajah, Janarthanan Wang, Binghe Zeng, Shelya Lu, Hua Nanoparticle encapsulation of non-genotoxic p53 activator Inauhzin-C for improved therapeutic efficacy |
title | Nanoparticle encapsulation of non-genotoxic p53 activator Inauhzin-C for improved therapeutic efficacy |
title_full | Nanoparticle encapsulation of non-genotoxic p53 activator Inauhzin-C for improved therapeutic efficacy |
title_fullStr | Nanoparticle encapsulation of non-genotoxic p53 activator Inauhzin-C for improved therapeutic efficacy |
title_full_unstemmed | Nanoparticle encapsulation of non-genotoxic p53 activator Inauhzin-C for improved therapeutic efficacy |
title_short | Nanoparticle encapsulation of non-genotoxic p53 activator Inauhzin-C for improved therapeutic efficacy |
title_sort | nanoparticle encapsulation of non-genotoxic p53 activator inauhzin-c for improved therapeutic efficacy |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171090/ https://www.ncbi.nlm.nih.gov/pubmed/34093867 http://dx.doi.org/10.7150/thno.57404 |
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