精胺
小干扰RNA
沟槽(工程)
螺旋(腹足类)
化学
细胞生物学
生物物理学
癌症研究
生物化学
转染
材料科学
生物
基因
酶
生态学
蜗牛
冶金
作者
Xiaoran Zhao,Qi Xu,Qian Wang,Xingxing Liang,Jing Wang,Hongwei Jin,Yizhi Man,Dongyang Guo,Feng Gao,Xinjing Tang
标识
DOI:10.1002/adhm.202303186
摘要
Abstract Gene therapy has been one of potential strategies for the treatment of different diseases, where efficient and safe gene delivery systems are also extremely in need. Current lipid nanoparticles (LNP) technology highly depends on the packing and condensation of nucleic acids with amine moieties. Here, an attempt to covalently link two natural compounds, spermine and vitamin E, is made to develop self‐assembled nucleic acid delivery systems. Among them, the spermine moieties specifically interact with the major groove of siRNA helix through salt bridge interaction, while vitamin E moieties are located around siRNA duplex. Such amphiphilic vitamin E‐spermine/siRNA complexes can further self‐assemble into nanocomplexes like multiblade wheels. Further studies indicate that these siRNA nanocomplexes with the neutrally charged surface of vitamin E can enter cells via caveolin/lipid raft mediated endocytosis pathway and bypass lysosome trapping. With these self‐assembled delivery systems, efficient siRNA delivery is successfully achieved for Eg5 and Survivin gene silencing as well as DNA plasmid delivery. Further in vivo study indicates that VE‐Su‐Sper/DSPE‐PEG 2000 /siSurvivin self‐assembled nanocomplexes can accumulate in cancer cells and gradually release siRNA in tumor tissues and show significant antitumor effect in vivo. The self‐assembled delivery system provides a novel strategy for highly efficient siRNA delivery.
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