title: Photodegradable neutral-cationic brush block copolymers for nonviral gene delivery.
abstract: We report on the fabrication of a photodegradable gene-delivery vector based on PEO-b-P(GMA-g-PDMAEMA) neutral-cationic brush block copolymers that possess cationic poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) brushes for DNA compaction, poly(ethylene oxide) (PEO) as a hydrophilic block, and poly(glycidyl methacrylate) (PGMA) as the backbone. The PEO-b-P(GMA-g-PDMAEMA) copolymers were synthesized through the combination of reversible addition-fragmentation transfer (RAFT) polymerization and postmodification. A photocleavable PEO-based macroRAFT agent was first synthesized; next, the PEO-b-PGMA block copolymer was prepared by RAFT polymerization of GMA; this was followed by a click reaction to introduce the RAFT initiators on the side chains of the PGMA block; then, RAFT polymerization of DMAEMA afforded the PEO-b-P(GMA-g-PDMAEMA) copolymer. The obtained neutral-cationic brush block copolymer could effectively complex plasmid DNA (pDNA) into nanoparticles at an N/P ratio (i.e., the number of nitrogen residues per DNA phosphate) of 4. Upon UV irradiation, pDNA could be released owing to cleavage of the pDNA-binding cationic PDMAEMA side chains as well as the nitrobenzyl ester linkages at the diblock junction point. In addition, in vitro gene transfection results demonstrated that the polyplexes could be effectively internalized by cells with good transfection efficiency, and the UV irradiation protocol could considerably enhance the efficiency of gene transfection.
authors.affiliation: Guangdong Institute of Microbiology, State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangzhou, Guangdong 510070 (China); 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), Fax: (+86) 551-6360-7348.
authors.forename: Xianglong
authors.initials: X
authors.lastname: Hu
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: Shiyong
authors.initials: S
authors.lastname: Liu
mesh_terms: D002412:Cations; D004247:DNA / Q000008:administration & dosage; D056945:Hep G2 Cells; D006801:Humans; D008823:Micelles; D008856:Microscopy, Fluorescence; D010957:Plasmids; D011108:Polymers / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D014162:Transfection / Q000379:methods*; D014466:Ultraviolet Rays
chemical_list: D002412:Cations; D008823:Micelles; D011108:Polymers; D004247:DNA
keywords: UV irradiation; block copolymers; gene technology; nitrobenzyl ester linkages; nonviral gene delivery