title: Bioreducible comb-shaped conjugates composed of secondary amine and hydroxyl group-containing backbones and disulfide-linked side chains with tertiary amine groups for facilitating gene delivery.
abstract: Comb-shaped polymeric vectors (SS-PGEADMs) consisting of ethanolamine/cystamine-functionalized poly(glycidyl methacrylate) (SS-PGEA-NH2) backbones and bioreducible poly((2-dimethyl amino)ethyl methacrylate) (PDMEAMA) side chains were prepared by a combination of the ring-opening reaction and atom transfer radical polymerization (ATRP). The SS-PGEA-NH2 backbones, which were prepared via the ring-opening reaction of the pendant epoxide groups of poly(glycidyl methacrylate) with the amine moieties of ethanolamine/cystamine, possess plentiful flanking secondary amine and hydroxyl groups and some flanking disulfide bond-containing cystamine derivatives. The primary amine groups of the cystamine derivatives were activated to produce bromoisobutylryl-terminated SS-PGEA (SS-PGEA-Br) as multifunctional initiators for subsequent ATRP of DMAEMA. The resultant disulfide-linked short PDMEAMA side chains possess pendant tertiary amine groups and are biocleavable. Such SS-PGEADMs can effectively condense pDNA. The cytotoxicity of SS-PGEADMs could be controlled by adjusting the grafting amount of PDMEAMA side chains. In comparison with the pristine SS-PGEA-NH2, the moderate introduction of PDMEAMA side chains can further enhance the gene transfection efficiency in different cell lines. The present approach to well-defined comb-shaped vectors with multifunctional groups could provide a versatile means for tailoring the functional structures of advanced gene/drug vectors.
authors: State Key Laboratory of Chemical Resource Engineering, Key Laboratory of Carbon Fiber and Functional Polymers, Ministry of Education, Beijing Laboratory of Biomedical Materials, College of Materials Science & Engineering, Beijing University of Chemical Technology , Beijing 100029, China.
authors: R Q
authors: RQ
authors: Li
authors: Y
authors: Y
authors: Hu
authors: B R
authors: BR
authors: Yu
authors: N N
authors: NN
authors: Zhao
authors: F J
authors: FJ
authors: Xu
mesh_terms: D000588:Amines / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004220:Disulfides / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000737:chemistry* / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D006878:Hydroxides / Q000737:chemistry*; D051379:Mice; D015394:Molecular Structure; D011109:Polymethacrylic Acids / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D004220:Disulfides; D006878:Hydroxides; D011109:Polymethacrylic Acids; C042535:polyglycidyl methacrylate; C031356:hydroxide ion