fulltext.study @t Gmail

A molecular dynamics simulation study on the effect of lipid substitution on polyethylenimine mediated siRNA complexation

Paper ID Volume ID Publish Year Pages File Format Full-Text
6305 476 2013 12 PDF Available
Title
A molecular dynamics simulation study on the effect of lipid substitution on polyethylenimine mediated siRNA complexation
Abstract

Polycations have been explored as non-viral carriers for effective delivery of small interfering RNA (siRNA). Modifying polycations such as polyethylenimine (PEI) with lipid substitution was found to improve the siRNA delivery efficiency of polycationic carriers. However, the role of such lipid modification is not clear and remains to be probed at the atomistic level. In this work, we elucidate the role of lipid modification through a series of all-atom molecular dynamics simulations on siRNA complexation mediated by a native PEI and four analogous obtained by different lipid modifications. The lipid modification does not affect PEI's capability of neutralizing the siRNA charge, neither does it affect the polyion bridging which plays an important role in siRNA complexation. Significant linkages among the lipid modified PEIs via association of lipid side-groups are observed and this results in more stable and compact PEI/siRNA polyplexes. The lipid associations between short lipids form and break frequently while the lipid associations between long lipids are more stable. For PEIs modified with short lipids, increasing the lipid substitution level results in more compact and stable siRNA structure. For PEIs modified with long lipids, increasing the lipid substitution does not change the amount of PEI linkage via lipid association, and has a reverse effect on compacting siRNA structure due to increased steric hindrance brought by the lipid association on individual PEIs. The simulation results generally correlate well with experimental data and suggest a framework of designing and systematic evaluation of polycation-based siRNA carriers using molecular dynamics simulations.

Keywords
siRNA; Polyethylenimine; Lipid; Molecular dynamics; Polyplex; Gene delivery
First Page Preview
A molecular dynamics simulation study on the effect of lipid substitution on polyethylenimine mediated siRNA complexation
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 34, Issue 11, April 2013, Pages 2822–2833
Authors
, , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering