Zhao Wei, Yang Yuping, Song Lingling, Kang Tianyi, Du Ting, Wu Yujiao, Xiong Meimei, Luo Li, Long Jianlin, Men Ke, Zhang Lan, Chen Xiaoxin, Huang Meijuan, Gou Maling
State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University, and Collaborative Innovation Center for Biotherapy Chengdu 610041 P. R. China.
Department of Thoracic Oncology Cancer Center and State Key Laboratory of Biotherapy West China Hospital West China Medical School Sichuan University Chengdu 610041 P. R. China.
Adv Sci (Weinh). 2017 Dec 29;5(3):1700263. doi: 10.1002/advs.201700263. eCollection 2018 Mar.
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 -[1-(2,3-dioleoyloxy) propyl]--trimethylammonium chloride (DOTAP) has low cytotoxicity and high transfection efficiency (>80%). Intraperitoneal administration of the p 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.
基因治疗为癌症治疗提供了一种新方法。本研究展示了一种受水疱性口炎病毒（VSV）启发的用于卵巢癌治疗的DNA纳米复合物。这种DNA纳米复合物由阳离子化的单甲氧基聚（乙二醇）-聚（d，l-丙交酯）（MPEG-PLA）纳米颗粒和编码水疱性口炎病毒基质蛋白（VSVMP）的质粒组成，VSVMP在VSV诱导癌细胞凋亡中起关键作用。由MPEG-PLA共聚物和-[1-（2,3-二油酰氧基）丙基]-三甲基氯化铵（DOTAP）自组装而成的阳离子化MPEG-PLA纳米颗粒具有低细胞毒性和高转染效率（>80%）。腹腔注射该p纳米复合物可显著抑制卵巢癌的腹腔转移，且不会引起明显的全身毒性。其抗癌机制涉及诱导凋亡和抗血管生成。这项工作展示了一种受VSV启发的DNA纳米复合物，它在治疗卵巢癌腹腔转移方面具有潜在应用价值。
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