Issue 19, 2022

Role of polyplex charge density in lipopolyplexes

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.

Graphical abstract: Role of polyplex charge density in lipopolyplexes

Supplementary files

Article information

Article type
Paper
Submitted
01 ธ.ค. 2564
Accepted
18 เม.ย. 2565
First published
19 เม.ย. 2565

Nanoscale, 2022,14, 7174-7180

Role of polyplex charge density in lipopolyplexes

J. Huang, W. Song, L. Meng, Y. Shen and R. Zhou, Nanoscale, 2022, 14, 7174 DOI: 10.1039/D1NR07897F

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements