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Targeted and Efficient Delivery of siRNA Using Tunable Polymeric Hybrid Micelles for Tumor Therapy.

作者信息

Hao Fei, Dong Shiyan, Yang Chunmiao, Li Ziwei, Cheng Ziyuan, Zhong Lihuang, Teng Lirong, Meng Qingfan, Lu Jiahui, Wu Fan, Xie Jing, Teng Lesheng, Lee Robert J

机构信息

School of Life Sciences, Jilin University, Changchun, P.R. China.

College of Medicine, Des Moines University, Des Moines, IA, U.S.A.

出版信息

Anticancer Res. 2019 Mar;39(3):1169-1178. doi: 10.21873/anticanres.13226.


DOI:10.21873/anticanres.13226
PMID:30842146
Abstract

BACKGROUND/AIM: Effective and targeted delivery of siRNA to tumor cells is a prerequisite to achieving their therapeutic effects. Survivin is up-regulated in tumor cells and is associated with resistance to therapy. Therefore, siRNA-mediated silencing of survivin is a potential therapeutic strategy for cancer. The aim of the study was to examine whether polymeric hybrid micelles can be used to effectively deliver siRNAs into cells. MATERIALS AND METHODS: First, linoleic acid (LA) was conjugated to polyethylenimine (PEI) and methoxy-polyethyleneglycol (mPEG) and two amphiphilic polymers (PEI-LA and mPEG-LA) were obtained. Polymeric hybrid micelle (PHM) was then prepared and characterized by self-assembly of PEI-LA and mPEG-LA at different percentages of the two amphiphilic polymers. A PHM/siRNA complex with optimized composition and good biocompatibility was then prepared and its cellular uptake, biodistribution, and antitumor effects were investigated. RESULTS: Survivin siRNA was efficiently delivered to the cells. It reduced survivin protein expression and greatly suppressed tumor growth. Moreover, siRNA loaded in PHM gathered in a solid tumor in mice and achieved an improved anticancer effect compared to naked siRNA. CONCLUSION: PHM is a promising and safe vehicle for siRNA delivery and may find utility in cancer therapy.

摘要

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