Cationic Methacrylate Copolymers Containing Primary and Tertiary Amino Side Groups: Controlled Synthesis via RAFT Polymerization, DNA Condensation, and In Vitro Gene Transfection

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A versatile family of cationic methacrylate copolymers containing varying amounts of primary and tertiary amino side groups were synthesized and investigated for in vitro gene transfection. Two different types of methacrylate copolymers, poly(2-(dimethylamino)ethyl methacrylate)/aminoethyl methacrylate [P(DMAEMA/AEMA)] and poly(2-(dimethylamino)ethyl methacrylate)/aminohexyl methacrylate [P(DMAEMA/AHMA)], were obtained by reversible addition-fragmentation chain transfer (RAFT) copolymerization of dimethylaminoethyl methacrylate (DMAEMA) with N-(tert-butoxycarbonyl)aminoethyl methacrylate (Boc-AEMA) or N-(tert-butoxycarbonyl)aminohexyl methacrylate (Boc-AHMA) followed by acid deprotection. Gel permeation chromatography (GPC) measurements revealed that Boc-protected methacrylate copolymers had M(n) in the range of 16.1-23.0 kDa and low polydispersities of 1.12-1.26. The copolymer compositions were well controlled by monomer feed ratios. Dynamic light scattering and agarose gel electrophoresis measurements demonstrated that these PDMAEMA copolymers had better DNA condensation than PDMAEMA homopolymer. The polyplexes of these copolymers revealed low cytotoxicity at an NIP ratio of 3/1. The in vitro transfection in COS-7 cells in serum free medium demonstrated significantly enhanced (up to 24-fold) transfection efficiencies of PDMAEMA copolymer polyplexes as compared with PDMAEMA control. In the presence of 10% serum, P(DMAEMA/AEMA) and P(DMAEMA/AHMA) displayed a high transfection activity comparable with or better than 25 kDa PEI. These results suggest that cationic methacrylate copolymers are highly promising for development of safe and efficient nonviral gene transfer agents. (C) 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2869-2877, 2010
Publisher
Wiley-Blackwell
Issue Date
2010-07
Language
English
Article Type
Article
Keywords

BIOREDUCIBLE POLY(AMIDO AMINE)S; TRIBLOCK COPOLYMERS; LOW CYTOTOXICITY; DELIVERY; POLYMERS; EFFICIENCY; CELLS; POLYPLEXES; COMPLEXES; MICELLES

Citation

JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY, v.48, no.13, pp.2869 - 2877

ISSN
0887-624X
DOI
10.1002/pola.24064
URI
http://hdl.handle.net/10203/93540
Appears in Collection
BS-Journal Papers(저널논문)
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