Yasuhide Nakayama, Takeshi Masuda, Makoto Nagaishi, Michiko Hayashi, Moto Ohira and Mariko Harada-Shiba Pages 53 - 57 ( 5 )
Nano-structured hyperbranched cationic star polymers, called star vectors, were molecularly designed for a novel gene delivery non-viral vector. The linear and 3, 4 or 6 branched water-soluble cationic polymers, which had same molecular weight of ca. 18,000, were synthesized by iniferter (initiator-transfer agent-terminator)-based photo-livingradical polymerization of 3-(N,N-dimethylamino)propyl acrylamide, initiated from respective multi-dithiocarbamatederivatized benzenes as an iniferter. All polymers produced polyion complexes polyplexes by mixing with pDNA (pGL3-control plasmid), in which the particle size was ca. 250 nm in diameter [the charge ratio < 2 / 1 (vevtor / pDNA)] and ca. 150 nm (the charge ratio > 2.5 / 1), and the ζ-potential was ca. +10 mV (the charge ratio > 1 / 1). When COS-1 cells were incubated with the polyplexes 12h after preparation under the charge ratio of 5 / 1, higher gene expression was obtained as an increase in branching, with a little cytotoxicity. The relative gene expression to the linear polymer was about 2, 5, and 10 times in 3-, 4-, and 6-branched polymers, respectively. The precise change in branching of polymers enabled the control of the gene transfer activity.
non-viral vector, star polymer, polyplex, branched polymer, gene transfection, molecular design
Department of Bioengineering, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan.