Star-Shaped Cationic Polymers by Atom Transfer Radical Polymerization from β-Cyclodextrin Cores for Nonviral Gene Delivery

Cationic polymers with low cytotoxicity and high transfection efficiency have attracted considerable attention as nonviral carriers for gene delivery. Herein, well-defined and star-shaped CDPD consisting of β-CD cores and P(DMAEMA) arms, and CDPDPE consisting of CDPD and P(PEGEEMA) end blocks (where...

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Bibliographic Details
Published in:Biomacromolecules 2009-02, Vol.10 (2), p.285-293
Main Authors: Xu, F. J, Zhang, Z. X, Ping, Y, Li, J, Kang, E. T, Neoh, K. G
Format: Article
Language:English
Subjects:
Applied sciences
Biological and medical sciences
Cyclodextrins
Dendrimers - chemical synthesis
Dendrimers - chemistry
Exact sciences and technology
General pharmacology
Medical sciences
Methacrylates
Molecular Structure
Nylons
Organic polymers
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Physicochemistry of polymers
Polyethylene Glycols
Polymers with particular properties
Preparation, kinetics, thermodynamics, mechanism and catalysts
Transfection - methods
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Summary:Cationic polymers with low cytotoxicity and high transfection efficiency have attracted considerable attention as nonviral carriers for gene delivery. Herein, well-defined and star-shaped CDPD consisting of β-CD cores and P(DMAEMA) arms, and CDPDPE consisting of CDPD and P(PEGEEMA) end blocks (where CD = cyclodextrin, P(DMAEMA) = poly(2-(dimethylamino)ethyl methacrylate), P(PEGEEMA) = poly(poly(ethylene glycol)ethyl ether methacrylate)) for gene delivery were prepared via atom transfer radical polymerization (ATRP) from the bromoisobutyryl-terminated β-CD core. The CDPD and CDPDPE exhibit good ability to condense plasmid DNA (pDNA) into 100−200 nm size nanoparticles with positive zeta potentials of 25−40 mV at nitrogen/phosphate (N/P) ratios of 10 or higher. CDPD and CDPDPE exhibit much lower cytotoxicity and higher gene transfection efficiency than high molecular weight P(DMAEMA) homopolymers. A comparison of the transfection efficiencies between CDPD and P(DMAEMA) homopolymer indicates that the unique star-shaped architecture involving the CD core can enhance the gene transfection efficiency. In addition to reducing cytotoxicity, the introduction of a biocompatible P(PEGEEMA) end block to the P(DMAEMA) arms in CDPDPE can further enhance the gene transfection efficiency.
ISSN:1525-7797
1526-4602
DOI:10.1021/bm8010165