Treatment of cervical cancer by si RNA-loaded chitosan-coated calcium phosphate nanoparticles

作     者：Piaopiao Li Yi Yan Haitao Zhang Ru Wang Huhu Han Jiancheng Wang 李飘飘;闫仪;张海涛;王茹;韩壶壶;王坚成

作者机构：Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery SystemsSchool of Pharmaceutical SciencesPeking University Health Science CenterBeijing 100191China School of Pharmaceutical SciencesCentral South UniversityChangshaHunan 410013China 

基　　金：National Natural Science Foundation of China(Grant No.81473158,81690264 and 81773650) the New Drug R&D program of China(Grant No.2018ZX09721003-004) the Opening Project of Key Laboratory of Drug Targeting and Drug Delivery System,Ministry of Education(Sichuan University) 

出 版 物：《Journal of Chinese Pharmaceutical Sciences》 (中国药学（英文版）)

年 卷 期：2018年第27卷第8期

页      码：517-529页

摘      要：In the present study, a chitosan-coated calcium phosphate nanoparticle（CS/CaP/siRNA NP） was developed to deliver si RNA for treatment of cervical cancer. The CS/CaP/siRNA NPs were prepared by the nano-precipitation method. The resulted NPs had a uniform spherical morphology with a size of ～194 nm and a zeta potential of ～＋27 mV. In vitro experiments demonstrated that these NPs could efficiently deliver si EGFR into Hela cells and significantly down-regulate the EGFR expression level, which was probably associated with enhanced cell adhesion of chitosan, leading to extended residence time of cell internalization. Then the internalized CS/CaP/siRNA NPs exhibited pH-responsive disassembly of NPs, resulting in the enhanced release of si RNA and rapid lysosomal escape into cytoplasm. Moreover, in vivo anticancer results showed that the CS/CaP/siRNA NPs had significant inhibitory effects on tumor growth after intratumoral injection in Hela tumor xenografted nude mice, accompanying with no obvious changes of body weight during the whole experimental period. All these results indicated that the CS/CaP/siRNA NPs would have great potential to deliver si RNA for the treatment of cervical cancer via mucosal administration.

主 题 词：siRNA delivery Chitosan Calcium phosphate pH-sensitive Cervical cancer 

学科分类：100702[100702] 1007[医学-药学类] 1006[医学-中西医结合类] 100602[100602] 10[医学] 

核心收录：

D　O　I：10.5246/jcps.2018.08.053

馆 藏 号：203325347...