转染
基因传递
DNA
细胞质
脂质双层
生物物理学
化学
细胞生物学
生物化学
分子生物学
基因
生物
膜
作者
Guowei Wang,Siqin Chen,Nasha Qiu,Bihan Wu,Dingcheng Zhu,Zhuxian Zhou,Ying Piao,Jianbin Tang,Youqing Shen
出处
期刊:Nano Today
[Elsevier]
日期:2021-08-01
卷期号:39: 101215-101215
被引量:28
标识
DOI:10.1016/j.nantod.2021.101215
摘要
Nonviral gene delivery vectors are promising alternatives to viral vectors, but their low transfection efficiency limits their applications. Mimicking virus transfection process has been attempted to enhance the nonviral gene delivery efficiency. Herein, we present a virus-mimicking polymeric vector capable of sticking onto the cell membrane and ejecting DNA into the cytoplasm for efficient gene transfection. This DNA-ejecting vector is advantageous in bypassing endo-/lysosomal DNA degradation, leading to high gene expression efficiency and avoiding the safety concerns of the internalized carrier materials. Linear polyethyleneimine is quaternized to carry N-[(p-acyloxybenzyloxycarbonyl)ethyl]-N-methyl ammonium, which is susceptible to esterase hydrolysis to water-soluble zwitterion. Optimizing the acyl chain lengths gives the polymer, L4 (acyl = octanoyl), which packs DNA into the nano-sized polyplex with pendant octanoyl chains. On contacting a cell, the octanoyl chains can insert into the lipid-bilayer and anchor the polyplex onto the cell membrane. The part of the polyplexes facing the cytoplasm exposes to cytosolic esterases, which hydrolyze the octanoyl esters and turn the polymer zwitterionic, thereby liberalizing the DNA to squeeze into the cytoplasm driven by free DNA's strong electrostatic repulsion. The polyplex coated with a poly(γ-glutamic acid) layer maintains the DNA-injection ability and has high efficiency for in vivo gene transfection.
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