title: A novel glutathione modified chitosan conjugate for efficient gene delivery.
abstract: A novel non-viral gene vector based on poly[poly(ethylene glycol) methacrylate] (PMPEG) and l-glutathione (GSH) grafted chitosan (CS) has been fabricated. First, well-defined brush-like PMPEG living polymers with dithioester residues were prepared by the reversible addition-fragmentation chain transfer (RAFT) polymerization and grafted onto the allylchitosan via radical coupling method. Then, the tripeptide GSH was introduced onto the end of PMPEG chain to give a CS-PMPEG-GSH conjugate. In comparison with pristine chitosan, CS-PMPEG-GSH conjugate could not only condense plasmid DNA (pDNA) and prevent the condensed CS-PMPEG-GSH/pDNA nanoparticle self-aggregation, but also increase the binding ability to cell membrane efficiently and improve decondensed ability of pDNA from the nanoparticles in cytoplasm which thus has resulted in the higher transfection efficiency in mouse embryonic fibroblast cells (NIH3T3). In addition, cytotoxicity assays showed that the conjugate is less cytotoxic than CS, and still retain the cationic polyelectrolyte characteristic as chitosan. These results indicate that the non-viral vector is a promising candidate for gene therapy in clinical application.
authors.affiliation: Key Laboratory of Functional Polymer Materials (Nankai University), Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Weijin Road, No. 94, Tianjin 300071, China.
authors.forename: Congxin
authors.initials: C
authors.lastname: Li
authors.forename: Tianying
authors.initials: T
authors.lastname: Guo
authors.forename: Dezhong
authors.initials: D
authors.lastname: Zhou
authors.forename: Yuling
authors.initials: Y
authors.lastname: Hu
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.forename: Shufang
authors.initials: S
authors.lastname: Wang
authors.forename: Jiatong
authors.initials: J
authors.lastname: Chen
authors.forename: Zhengpu
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry*; D018014:Gene Transfer Techniques / Q000639:trends*; D005978:Glutathione / Q000008:administration & dosage* / Q000737:chemistry* / Q000235:genetics; D051379:Mice; D041681:NIH 3T3 Cells; D016896:Treatment Outcome
chemical_list: D048271:Chitosan; D005978:Glutathione