Tumor-targeted redox-responsive nonviral gene delivery nanocarriers based on neutral-cationic brush block copolymers

Novel neutral-cationic brush block copolymer, poly[oligo(ethylene glycol) monomethyl ether methacrylate-co-folic acid methacrylate]-b-poly[2-(2-(2-(2- bromo-2-methylpropanoyloxy)-ethyl) disulfanyl) ethyl methacrylate-g-2- dimethylaminoethyl methacrylate], P(OEGMA-co-FAMA)-b-P(BSSMA-g-PDMAEMA), is synthesized via consecutive controlled radical polymerizations. Containing disulfide linkages bridging backbone and side chains in the cationic brush block and cancer cell-targeting ligands (folic acid) in the neutral hydrophilic block, the diblock copolymer is employed as a tumor-targeted redox-responsive degradable nonviral gene delivery vector. P(OEGMA-co-FAMA)-b-P(BSSMA-g-PDMAEMA) brush block copolymers can condense plasmid DNA (pDNA) efficiently via the formation of electrostatic polyplex micelles. Under reductive milieu, pDNA can be released due to the cleavage of disulfide linkages and accordingly pDNA-binding cationic PDMAEMA side chains. In addition, the brush block copolymer exhibits low cytotoxicity and the corresponding polyplex micelles show relatively high gene transfection efficiency. Novel neutral-cationic brush block copolymers containing targeting ligands and disulfide linkages are synthesized and utilized as tumor-targeted redox-responsive and biodegradable nonviral gene delivery vectors for lower cytotoxicity and high gene transfection efficiency.