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 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 P-CD core. The CDPD and CDPDPE exhibit good ability to condense plasmid DNA (pDNA) into 100-200 rim 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.