Restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of PTEN mRNA Journal Article

Authors: Islam, M. A.; Xu, Y.; Tao, W.; Ubellacker, J. M.; Lim, M.; Aum, D.; Lee, G. Y.; Zhou, K.; Zope, H.; Yu, M.; Cao, W.; Oswald, J. T.; Dinarvand, M.; Mahmoudi, M.; Langer, R.; Kantoff, P. W.; Farokhzad, O. C.; Zetter, B. R.; Shi, J.
Article Title: Restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of PTEN mRNA
Abstract: 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. © 2018, The Author(s).
Keywords: cell death; rna; tumors; nucleic acids; urology; nanoparticles; molecular biology; diseases; phosphatidylinositol 3-kinase; restoration; prostate cancer cells; proof of principles; hybrid nanoparticle; messenger rnas (mrna); mrna transfection; phosphatase and tensin homologue deleted on chromosome 10; tumour suppressor genes
Journal Title: Nature Biomedical Engineering
Volume: 2
Issue: 11
ISSN: 2157-846X
Publisher: Nature Publishing Group  
Date Published: 2018-11-01
Start Page: 850
End Page: 864
Language: English
DOI: 10.1038/s41551-018-0284-0
PROVIDER: scopus
Notes: Erratum issued, see DOI: 10.1038/s41551-018-0331-x -- Export Date: 3 December 2018 -- Source: Scopus
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  1. Philip Wayne Kantoff
    62 Kantoff