Insights into the endosomal escape mechanism via investigation of dendrimer-membrane interactions
Insights into the endosomal escape mechanism via investigation of dendrimer-membrane interactions
复制标题
通过研究树枝状聚合物与膜相互作用深入了解内体逃逸机制
DOI：
10.1039/c2sm25538c
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发表时间：
2012-01-01
期刊：
影响因子：
3.4
通讯作者：
Ma, Yu-qiang
中科院分区：
文献类型：
--
作者：
Tian, Wen-de;Ma, Yu-qiang
了解非病毒载体从内体逃逸的机制对于开发新的基因递送系统至关重要。粗粒度的分子动力学模拟响应树枝状大分子与张力和紧张的脂质膜相互作用进行深入了解基因逃逸机制。有人发现，带电的树枝状聚合物插入到膜中是由带电的脂质的不对称分布和强带电的树枝状聚合物可以导致膜的不对称性的故障促进。此外，树枝状聚合物吸附可能导致破坏膜所需的临界应力下降。我们提出，纳米粒子穿透靶向膜的一个基本途径是赋予它们调节局部膜张力的能力。最后，提出了一种基因材料从内体逃逸的机制：渗透压和树枝状聚合物在内体中的尺寸增加引起的全局效应和树枝状聚合物静电吸附引起的局部效应之间的协同作用。
Understanding the mechanism of the escape of non-viral vectors from endosomes is critically important for the development of new gene delivery systems. Coarse-grained molecular dynamics simulations of responsive dendrimers interacting with tensionless and tense lipid membranes were performed to give insight into the gene escape mechanism. It was found that the insertion of a charged dendrimer into a membrane is facilitated by the asymmetric distribution of charged lipids and the strongly charged dendrimer can cause a breakdown of membrane asymmetry. Furthermore, dendrimer adsorption could lead to the drop of critical stress required to disrupt the membrane. We propose that a fundamental way for nanoparticles to penetrate through targeted membranes is endowing them with capabilities to tune the local membrane tension. Finally, an escape mechanism of delivered gene materials from an endosome was suggested: a cooperation between global effect, resulting from osmotic pressure and the increase of dendrimer size in the endosome, and local effects caused by the electrostatic adsorption of dendrimers.