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
School of Life Sciences, Jilin University, Changchun, P.R. China.
College of Medicine, Des Moines University, Des Moines, IA, U.S.A.
Anticancer Res. 2019 Mar;39(3):1169-1178. doi: 10.21873/anticanres.13226.
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.
Int J Nanomedicine. 2021
Acta Pharm Sin B. 2020-11
Front Bioeng Biotechnol. 2020-6-11