High performance gene delivery polymeric vector: nano-structured cationic star polymers (star vectors).
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-living-radical polymerization of 3-(N,N-dimethylamino)propyl acrylamide, initiated from respective multi-dithiocarbamate-derivatized 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 zeta-potential was ca. +10 mV (the charge ratio > 1/1). When COS-1 cells were incubated with the polyplexes 12 h 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.
Nakayama
Yasuhide
Y
Department of Bioengineering, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan. nakayama@ri.ncvc.go.jp
Masuda
Takeshi
T
Nagaishi
Makoto
M
Hayashi
Michiko
M
Ohira
Moto
M
Harada-Shiba
Mariko
M
D000818:Animals; D019556:COS Cells; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D015195:Drug Design; D015870:Gene Expression / Q000187:drug effects; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage / Q000737:chemistry* / Q000235:genetics; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D049329:Nanostructures / Q000737:chemistry*; D011108:Polymers / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods
D011108:Polymers; D008156:Luciferases