文献类型：期刊文章

作　　者：杨梦依[1,2] 孙晶[1,2] 王超[1,2] 张艳芬[1,2] 张礼和[1,2] 杨振军[1,2]

机构地区：[1]北京大学医学部药学院天然药物及仿生药物国家重点实验室 [2]北京大学医学部药学院药物化学系,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》

基　　金：The National Natural Science Foundation of China(Grant No.21778006 and 20932001);the Ministry of Science and Technology of China(Grant No.2012AA022501)

年　　份：2017

卷　　号：26

期　　号：10

起止页码：719-726

语　　种：中文

收录情况：CAB、CAS、CSCD、CSCD2017_2018、DOAJ、EMBASE、IC、JST、SCOPUS、ZGKJHX、普通刊

摘　　要：Cationic lipids have been applied to siRNA delivery for tumor therapeutics. However, the excess positive charges of these nanoplexes may lead to high cytotoxicity and nonnegligible immunogenicity both in vitro and in vivo, which limited the applications of gene drugs. We constructed multi-component lipoplex to delivery 3＇,3＂-bis-peptide-siRNA conjugate （pp-siRNA） by the treatment of melanoma. Based on the previous studies that the gemini lipid （CLD） encapsulated pp-siRNA, a novel neutral cytosin-l-yl- lipid （DNCA） was considered to replace a certain ration of CLD by hydrogen bonds and ~t-n stacking for reducing the cytotoxicity. It similarly retained in both the loading efficiency and targeted mRNA inhibition when DNCA was accounted for 40% in the lipoplex, with lower toxicity. Moreover, CLD/DNCA/pp-siRNA nanoplex could be uptake in A375 cells and internalized mainly by macropinocytosis and caveolin-mediated endocytosis. Besides, 90% CLD/DNCA/pp-siRNA nanoplexes presented the highest efficient knockdown for the mutant B-RAF mRNA （-80%）. All the results demonstrated that the mixed cationic and neutral lipids could efficiently realize the delivery of pp-siRNA and had potential application for cancer therapy.

关 键 词：3＇,3＂-Bis-peptide siRNA conjugate  Gemini-like cationic lipid  Cytosin-1-yl-lipid  Melanoma therapy  

分 类 号：R945]