A Vesicular Stomatitis Virus-Inspired DNA Nanocomplex for Ovarian Cancer Therapy

受水泡性口炎病毒启发的 DNA 纳米复合物用于卵巢癌治疗

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作者:Wei Zhao, Yuping Yang, Lingling Song, Tianyi Kang, Ting Du, Yujiao Wu, Meimei Xiong, Li Luo, Jianlin Long, Ke Men, Lan Zhang, Xiaoxin Chen, Meijuan Huang, Maling Gou

Abstract

Gene therapy provides a novel method for cancer therapy. This study shows a DNA nanocomplex that is inspired from vesicular stomatitis virus (VSV) for ovarian cancer therapy. This DNA nanocomplex consists of a cationized monomethoxy poly (ethylene glycol)-poly (d,l-lactide) (MPEG-PLA) nanoparticle and a plasmid encoding the matrix protein of vesicular stomatitis virus (VSVMP) that plays a critical role in the VSV-induced apoptosis of cancer cells. The cationized MPEG-PLA nanoparticle that is self-assembled by MPEG-PLA copolymer and N -[1-(2,3-dioleoyloxy) propyl]-N,N,N-trimethylammonium chloride (DOTAP) has low cytotoxicity and high transfection efficiency (>80%). Intraperitoneal administration of the p VSVMP nanocomplex remarkably inhibits the intraperitoneal metastasis of ovarian cancer and does not cause significant systemic toxicity. The apoptosis induction and anti-angiogenesis are involved in the anticancer mechanism. This work demonstrates a VSV-inspired DNA nanocomplex that has potential application for the treatment of intraperitoneal metastasis of ovarian cancer.

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