Open AccessPoly(ethylene glycol) Crowding as Critical Factor To Determine pDNA Packaging Scheme into Polyplex Micelles for Enhanced Gene Expression
Author(s) -
Kaori M. Takeda,
Kensuke Osada,
Theofilus A. Tockary,
Anjaneyulu Dirisala,
Qixian Chen,
Kazunori Kataoka
Publication year - 2016
Publication title -
biomacromolecules
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.689
H-Index - 220
eISSN - 1526-4602
pISSN - 1525-7797
DOI - 10.1021/acs.biomac.6b01247
Subject(s) - peg ratio , polyethylene glycol , chemistry , micelle , ethylene glycol , biophysics , gene delivery , steric effects , gene expression , transfection , chemical engineering , polymer chemistry , gene , biochemistry , stereochemistry , organic chemistry , aqueous solution , biology , finance , engineering , economics
A critical role of polyethylene glycol (PEG) crowding in the packaging of plasmid DNA (pDNA) into polyplex micelles (PMs) was investigated using a series of PEG-b-poly(l-lysine) (PEG-PLys) block copolymers with varying molecular weights of both PEG and PLys segments. Rod-shaped PMs preferentially formed when the tethered PEG chains covering pDNA in a precondensed state were dense enough to overlap one another (reduced tethering density (RTD) > 1), whereas globular PMs were obtained when they were not overlapped (RTD < 1). These results submitted a scheme that steric repulsive effect of PEG regulated packaging pathways of pDNA either through folding into rod-shape or collapsing into globular depending on whether the PEG chains are overlapped or not. The rod-shaped PMs gave significantly higher gene expression efficacies in a cell-free system compared to the globular PMs, demonstrating the practical relevance of regulating packaging structure of pDNA for developing efficient gene delivery systems.