Restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of PTEN mRNA
© 2018, The Author(s). Phosphatase and tensin homologue deleted on chromosome 10 (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 tr...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Springer Science and Business Media LLC
2021
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| Online Access: | https://hdl.handle.net/1721.1/135009 |
| _version_ | 1826208821377236992 |
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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 |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT 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 | MIT |
| description | © 2018, The Author(s). Phosphatase and tensin homologue deleted on chromosome 10 (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 messenger RNA (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 polyethylene glycol shell. The nanoparticles are stable in serum, elicit low toxicity and enable high PTEN mRNA transfection in prostate cancer cells. Moreover, significant inhibition of tumour growth is achieved 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 phosphatidylinositol 3-kinase (PI3K)–AKT pathway and enhances apoptosis. Our findings provide proof-of-principle evidence of the restoration of mRNA-based tumour suppression in vivo. |
| first_indexed | 2024-09-23T14:13:08Z |
| format | Article |
| id | mit-1721.1/135009 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:13:08Z |
| publishDate | 2021 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1350092024-03-20T19:10:18Z 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 Koch Institute for Integrative Cancer Research at MIT Massachusetts Institute of Technology. Institute for Medical Engineering & Science © 2018, The Author(s). Phosphatase and tensin homologue deleted on chromosome 10 (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 messenger RNA (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 polyethylene glycol shell. The nanoparticles are stable in serum, elicit low toxicity and enable high PTEN mRNA transfection in prostate cancer cells. Moreover, significant inhibition of tumour growth is achieved 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 phosphatidylinositol 3-kinase (PI3K)–AKT pathway and enhances apoptosis. Our findings provide proof-of-principle evidence of the restoration of mRNA-based tumour suppression in vivo. 2021-10-27T20:10:17Z 2021-10-27T20:10:17Z 2018 2019-09-03T17:05:37Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135009 en 10.1038/S41551-018-0284-0 Nature Biomedical Engineering Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Springer Science and Business Media LLC PMC |
| spellingShingle | 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 |
| url | https://hdl.handle.net/1721.1/135009 |
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