Star-shaped cationic polymers by atom transfer radical polymerization from beta-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 beta-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 beta-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.
Xu
F J
FJ
College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029 China. xufj@mail.buct.edu.cn
Zhang
Z X
ZX
Ping
Y
Y
Li
J
J
Kang
E T
ET
Neoh
K G
KG
D003505:Cyclodextrins; D050091:Dendrimers / Q000138:chemical synthesis* / Q000737:chemistry; D008689:Methacrylates; D015394:Molecular Structure; D009757:Nylons; D011092:Polyethylene Glycols; D014162:Transfection / Q000379:methods*
D003505:Cyclodextrins; D050091:Dendrimers; D008689:Methacrylates; D009757:Nylons; C407037:poly(2-(dimethylamino)ethyl methacrylate); C524499:polyethylene glycol methacrylate; D011092:Polyethylene Glycols