Comb-Shaped Copolymers Composed of Hydroxypropyl Cellulose Backbones and Cationic Poly((2-dimethyl amino)ethyl methacrylate) Side Chains for Gene Delivery

Cationic polymers have been of interest and importance as nonviral gene delivery carriers. Herein, well-defined comb-shaped cationic copolymers (HPDs) composed of long biocompatible hydroxypropyl cellulose (or HPC) backbones and short poly((2-dimethyl amino)ethyl methacrylate) (or P(DMAEMA)) side ch...

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Bibliographic Details
Published in:Bioconjugate chemistry 2009-08, Vol.20 (8), p.1449-1458
Main Authors: Xu, F. J, Ping, Y, Ma, J, Tang, G. P, Yang, W. T, Li, J, Kang, E. T, Neoh, K. G
Format: Article
Language:English
Subjects:
Ammonia
Biochemistry
Biopolymers
Cations - chemistry
Cations - pharmacology
Cell Line
Cell Survival - drug effects
Cellulose - analogs & derivatives
Cellulose - chemistry
Cellulose - pharmacology
Chemicals
Deoxyribonucleic acid
DNA
DNA - chemistry
DNA - isolation & purification
Gene Transfer Techniques
Genes
Genetic Vectors - chemistry
Genetic Vectors - pharmacology
Humans
Methacrylates - chemistry
Methacrylates - pharmacology
Nanoparticles - chemistry
Nylons - chemistry
Nylons - pharmacology
Plasmids - chemistry
Plasmids - isolation & purification
Quaternary Ammonium Compounds - chemical synthesis
Quaternary Ammonium Compounds - chemistry
Quaternary Ammonium Compounds - pharmacology
Structure-Activity Relationship
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Summary:Cationic polymers have been of interest and importance as nonviral gene delivery carriers. Herein, well-defined comb-shaped cationic copolymers (HPDs) composed of long biocompatible hydroxypropyl cellulose (or HPC) backbones and short poly((2-dimethyl amino)ethyl methacrylate) (or P(DMAEMA)) side chains were prepared as gene vectors via atom transfer radical polymerization (ATRP) from the bromoisobutyryl-terminated HPC biopolymers. The P(DMAEMA) side chains of HPDs can be further partially quaternized to produce the quaternary ammonium HPDs (QHPDs). HPDs and QHPDs were assessed in vitro for nonviral gene delivery. HPDs exhibit much lower cytotoxicity and better gene transfection yield than high-molecular-weight P(DMAEMA) homopolymers. QHPDs exhibit a stronger ability to complex pDNA, due to increased surface cationic charges. Thus, the approach to well-defined comb-shaped cationic copolymers provides a versatile means for tailoring the functional structure of nonviral gene vectors to meet the requirements of strong DNA-condensing ability and high transfection capability.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc900044h