title: Tumor-targeted redox-responsive nonviral gene delivery nanocarriers based on neutral-cationic brush block copolymers.
abstract: 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.
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Guoying
authors.initials: G
authors.lastname: Zhang
authors.forename: Zhishen
authors.initials: Z
authors.lastname: Ge
authors.forename: Shiyong
authors.initials: S
authors.lastname: Liu
mesh_terms: D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D008689:Methacrylates / Q000737:chemistry; D008823:Micelles; D049329:Nanostructures / Q000737:chemistry*; D009757:Nylons / Q000737:chemistry; D010084:Oxidation-Reduction; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
chemical_list: D001672:Biocompatible Materials; D008689:Methacrylates; D008823:Micelles; D009757:Nylons; D011108:Polymers; C407037:poly(2-(dimethylamino)ethyl methacrylate)
keywords: biodegradable; brush block copolymers; gene delivery; reductive milieu; stimuli-responsive polymers