阳离子脂质体
脂质体
化学
PEG比率
内体
基因沉默
转染
生物物理学
小干扰RNA
基因传递
阳离子聚合
体内
毒品携带者
体外
细胞生物学
分子生物学
药物输送
生物化学
细胞
生物
高分子化学
生物技术
有机化学
财务
基因
经济
作者
Yan Li,Qiang Cheng,Jiang Qian,Yuanyu Huang,Hongmei Li,Ye Zhao,Weipeng Cao,Guanghui Ma,Fengying Dai,Xing-Jie Liang,Zicai Liang,Xin Zhang
标识
DOI:10.1016/j.jconrel.2013.12.007
摘要
Cationic liposome based siRNA delivery system has improved the efficiencies of siRNA. However, cationic liposomes are prone to be rapidly cleared by the reticuloendothelial system (RES). Although modification of cationic liposomes with polyethylene glycol (PEG) could prolong circulation lifetime, PEG significantly inhibits siRNA entrapment efficiency, cellular uptake and endosomal/lysosomal escape process, resulting in low gene silencing efficiency of siRNA. In this study, we report the synthesis of zwitterionic polycarboxybetaine (PCB) based distearoyl phosphoethanolamine-polycarboxybetaine (DSPE-PCB) lipid for cationic liposome modification. The DSPE-PCB20 cationic liposome/siRNA complexes (lipoplexes) show an excellent stability in serum medium. The siRNA encapsulation efficiency of DSPE-PCB20 lipoplexes could reach 92% at N/P ratio of 20/1, but only 73% for DSPE-PEG lipoplexes. The zeta potential of DSPE-PCB20 lipoplexes is 8.19±0.53mV at pH 7.4, and increases to 24.6±0.87mV when the pH value is decreased to 4.5, which promotes the endosomal/lysosomal escape of siRNA. The DSPE-PCB20 modification could enhance the silencing efficiency of siRNA by approximately 20% over the DSPE-PEG 2000 lipoplexes at the same N/P ratio in vitro. Furthermore, DSPE-PCB20 lipoplexes could efficiently mediate the down-regulation of Apolipoprotein B (ApoB) mRNA in the liver and consequently decrease the total cholesterol in the serum in vivo, suggesting therapeutic potentials for siRNA delivery in hypercholesterolemia-related diseases.
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