Restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of PTEN mRNA
Name
nihms-1502267.pdf
Description
Accepted version
Size
3.77 MB
Format
Adobe PDF
Checksum (MD5)
bfda42f06255030d792cbbcfcb3124b6
Author(s)
Islam, Mohammad Ariful
Xu, Yingjie
Tao, Wei
Ubellacker, Jessalyn M
Lim, Michael
Aum, Daniel
Lee, Gha Young
Zhou, Kun
Zope, Harshal
Yu, Mikyung
Date Issued
2018
Journal
Nature Biomedical Engineering
Publisher
Springer Science and Business Media LLC
Version
Author's final manuscript
Abstract
© 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.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Terms of Use
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.
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DOI of Published Version
10.1038/S41551-018-0284-0
https://doi.org/10.1038/S41551-018-0284-0
