Cationic switchable lipids: pH-triggered molecular switch for siRNA delivery

被引:45
作者
Viricel, W. [1 ]
Poirier, S. [2 ]
Mbarek, A. [1 ]
Derbali, R. M. [1 ]
Mayer, G. [1 ,2 ]
Leblond, J. [1 ]
机构
[1] Univ Montreal, Fac Pharm, Downtown Stn, POB 6128, Montreal, PQ, Canada
[2] Montreal Heart Inst, Lab Mol Cell Biol, Montreal, PQ H1T 1C8, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
IN-VIVO; ENDOSOMAL ESCAPE; NONHUMAN-PRIMATES; NANOPARTICLES; CANCER; THERAPEUTICS; POTENCY; SIZE; RNAI; EFFICIENCY;
D O I
10.1039/c6nr06701h
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A pH-sensitive molecular switch able to change its conformation upon protonation at endosomal pH values is embedded into the structure of cationic lipidoid materials, thus conferring endosomal escape properties. Involvement of the conformational switch in the endosomal escape process was confirmed and leading material identified was able to induce efficient gene knockdown both in vitro and in vivo. The lipid nanoparticles reported here are promising for therapeutic applications and this work could serve as a template for future design of stimulus-responsive (ionic, redox, light) molecular switch for drug and gene delivery.
引用
收藏
页码:31 / 36
页数:6
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