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Restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of PTEN mRNA
PTEN is a well-characterized tumour-suppressor gene that is lost or mutated in about half of metastatic castration-resistant prostate cancers and in many other human cancers. The restoration of functional PTEN as a treatment for prostate cancer has however proven difficult. Here, we show that PTEN m...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486184/ https://www.ncbi.nlm.nih.gov/pubmed/31015614 http://dx.doi.org/10.1038/s41551-018-0284-0 |
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author | Islam, Mohammad Ariful Xu, Yingjie Tao, Wei Ubellacker, Jessalyn M. Lim, Michael Aum, Daniel Lee, Gha Young Zhou, Kun Zope, Harshal Yu, Mikyung Cao, Wuji Oswald, James Trevor Dinarvand, Meshkat Mahmoudi, Morteza Langer, Robert Kantoff, Philip W. Farokhzad, Omid C. Zetter, Bruce R. Shi, Jinjun |
author_facet | Islam, Mohammad Ariful Xu, Yingjie Tao, Wei Ubellacker, Jessalyn M. Lim, Michael Aum, Daniel Lee, Gha Young Zhou, Kun Zope, Harshal Yu, Mikyung Cao, Wuji Oswald, James Trevor Dinarvand, Meshkat Mahmoudi, Morteza Langer, Robert Kantoff, Philip W. Farokhzad, Omid C. Zetter, Bruce R. Shi, Jinjun |
author_sort | Islam, Mohammad Ariful |
collection | PubMed |
description | PTEN is a well-characterized tumour-suppressor gene that is lost or mutated in about half of metastatic castration-resistant prostate cancers and in many other human cancers. The restoration of functional PTEN as a treatment for prostate cancer has however proven difficult. Here, we show that PTEN mRNA can be reintroduced into PTEN-null prostate cancer cells in vitro and in vivo via its encapsulation in polymer-lipid hybrid nanoparticles coated with a poly(ethylene glycol) shell. The nanoparticles are stable in serum, elicit low toxicity, enable high PTEN mRNA transfection in prostate cancer cells, and lead to significant inhibition of tumour growth when delivered systemically in multiple mouse models of prostate cancer. We also show that the restoration of PTEN function in PTEN-null prostate cancer cells inhibits the PI3K-AKT pathway and enhances apoptosis. Our findings provide proof-of-principle evidence of the restoration of mRNA-based tumour suppression in vivo. |
format | Online Article Text |
id | pubmed-6486184 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
record_format | MEDLINE/PubMed |
spelling | pubmed-64861842019-04-26 Restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of PTEN mRNA Islam, Mohammad Ariful Xu, Yingjie Tao, Wei Ubellacker, Jessalyn M. Lim, Michael Aum, Daniel Lee, Gha Young Zhou, Kun Zope, Harshal Yu, Mikyung Cao, Wuji Oswald, James Trevor Dinarvand, Meshkat Mahmoudi, Morteza Langer, Robert Kantoff, Philip W. Farokhzad, Omid C. Zetter, Bruce R. Shi, Jinjun Nat Biomed Eng Article PTEN is a well-characterized tumour-suppressor gene that is lost or mutated in about half of metastatic castration-resistant prostate cancers and in many other human cancers. The restoration of functional PTEN as a treatment for prostate cancer has however proven difficult. Here, we show that PTEN mRNA can be reintroduced into PTEN-null prostate cancer cells in vitro and in vivo via its encapsulation in polymer-lipid hybrid nanoparticles coated with a poly(ethylene glycol) shell. The nanoparticles are stable in serum, elicit low toxicity, enable high PTEN mRNA transfection in prostate cancer cells, and lead to significant inhibition of tumour growth when delivered systemically in multiple mouse models of prostate cancer. We also show that the restoration of PTEN function in PTEN-null prostate cancer cells inhibits the PI3K-AKT pathway and enhances apoptosis. Our findings provide proof-of-principle evidence of the restoration of mRNA-based tumour suppression in vivo. 2018-09-17 2018-11 /pmc/articles/PMC6486184/ /pubmed/31015614 http://dx.doi.org/10.1038/s41551-018-0284-0 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Islam, Mohammad Ariful Xu, Yingjie Tao, Wei Ubellacker, Jessalyn M. Lim, Michael Aum, Daniel Lee, Gha Young Zhou, Kun Zope, Harshal Yu, Mikyung Cao, Wuji Oswald, James Trevor Dinarvand, Meshkat Mahmoudi, Morteza Langer, Robert Kantoff, Philip W. Farokhzad, Omid C. Zetter, Bruce R. Shi, Jinjun Restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of PTEN mRNA |
title | Restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of PTEN mRNA |
title_full | Restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of PTEN mRNA |
title_fullStr | Restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of PTEN mRNA |
title_full_unstemmed | Restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of PTEN mRNA |
title_short | Restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of PTEN mRNA |
title_sort | restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of pten mrna |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486184/ https://www.ncbi.nlm.nih.gov/pubmed/31015614 http://dx.doi.org/10.1038/s41551-018-0284-0 |
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