文献：脂质复合物中复合物电荷密度的作用

链接：https://pubs.rsc.org/en/content/articlelanding/2022/nr/d1nr07897f/unauth

作者：黄健翔，宋伟，孟丽君，沉有庆，周如红

摘要：

脂质复合物近年来在基因*领域备受关注。然而，复合物与脂质体之间的相互作用及其潜在的分子机制仍有待进一步阐明。本文，我们采用了一个简单的模型，主要通过粗粒度分子动力学模拟来阐明复合物电荷密度对脂质体（包含DOPE和CHEMS脂质）自组装的影响。模拟结果表明，当复合物中电荷密度增加时，更多的脂质，尤其是CHEMS（一种带负电荷的辅助脂质）脂质，会被吸引到复合物（带正电荷）表面，同时附近的水分子会被驱离复合物，导致脂质体的球形度降低。能量分解分析进一步表明，在较高的电荷密度下，复合物与CHEMS脂质的相互作用远强于与水分子的相互作用，其中大部分来自静电相互作用。此外，随着复合物电荷密度的增加，脂质（尤其是CHEMS）的迁移率降低，表明脂质体更加刚性。总而言之，我们的分子动力学模拟在原子水平上阐明了复合物电荷密度对脂质体自组装过程的影响，这为更好地理解这种有前景的基因*递送系统提供了一种补充实验方法。

Abstract

Lipopolyplexes have received extensive attention lately in gene therapy delivery. However, the interactions between the polyplex and the liposome and their underlying molecular mechanisms remain to be elucidated. Here, we adopted a simple model, mainly to illustrate the impact of polyplex charge density on the self-assembly of liposomes (containing DOPE and CHEMS lipids) using coarse-grained molecular dynamics simulations. Our simulation results show that when the charge density increases in the polyplex, more lipids, especially CHEMS (a negatively charged helper lipid) lipids, are attracted to the polyplex (positively charged) surface, and meanwhile nearby water molecules are driven away from the polyplex, resulting in a less spherical liposome. Energy decomposition analyses further reveal that, at higher charge densities, the polyplex exhibits much stronger interactions with CHEMS lipids than with water molecules, with the majority contribution from electrostatic interactions. In addition, the mobility of lipids, especially CHEMS, is reduced as the polyplex charge density increases, indicating a more rigid liposome. Overall, our molecular dynamics simulations elucidate the influence of polyplex charge density on the liposome self-assembly process at the atomic level, which provides a complementary approach to experiments for a better understanding of this promising gene therapy delivery system.

西安齐岳生物提供相关产品：

DSPE-PEG-多肽（各种定制）

DSPE-PEG-RGD 

DSPE-PEG-c(RGDfk)

DSPE-PEG-c(RGDfK)-FITC

DSPE-PEG-c(RGDfK)-Biotin

DSPE-PEG-c(RGDfc)

以上文章内容来源各类期刊或文献，如有侵权请联系我们删除！