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J Biomed Nanotechnol. 2018 Dec 1;14(12):2092-2101. doi: 10.1166/jbn.2018.2641.

Self-Assembled Nanoparticle Mediated Survivin-T34A for Ovarian Cancer Therapy.

Abstract

Gene therapy is emerging as a promising tool for cancer treatment. Down-regulation of survivin gene can lead to the cancer inhibition. However, the lack of efficient and safe gene delivery system is still a critical obstacle to clinical gene therapy. In this study, we use a biodegradable nanoparticle to deliver human survivin-T34A (T34A) to dominant-negatively regulate survivin gene for ovarian cancer therapy. This nanoparticle, self-assembled from monomethoxy poly(ethylene glycol)-poly(D,L-lactide) (MPEG-PLA) copolymer and N-[1-(2,3-dioleoyloxy) propyl]-N,N,N-trimethylammonium chloride (DOTAP), has high transfection capability and negligible cytotoxicity. The nanoparticle-delivered T34A gene can efficiently inhibit the growth of SKOV3 ovarian cancer cells through induction of apoptosis in vitro. After intraperitoneal injection, the nanoparticle-delivered T34A gene significantly inhibited the growth of intraperitoneal metastasis of SKOV3 ovarian cancer, with no obvious adverse effects. Our data suggest that the nanoparticle-delivered T34A gene has promising clinical applications in ovarian cancer treatment.

PMID:
30305216
DOI:
10.1166/jbn.2018.2641
[Indexed for MEDLINE]

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