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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
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.
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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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