title: Ring-opening polymerization for hyperbranched polycationic gene delivery vectors with excellent serum tolerance.
abstract: In order to improve the transfection efficiency (TE) and biocompatibility, we synthesized a series of hyperbranched cationic polymers by ring-opening polymerization between diepoxide and several polyamines. These materials can condense plasmid DNA efficiently into nanoparticles that have much lower cytotoxicity than those derived from bPEI. In vitro transfection experiments showed that polymers prepared from branched or cyclic polyamine (P1 and P5) exhibited TE several times higher than 25KDa bPEI. More significantly, serum seemed to have no negative effect on P1-P5 mediated transfection. On the contrary, the TE of P1 improved, even when the serum concentration reached 70%. Several assays demonstrated the excellent serum tolerance of such polycationic vectors: bovine serum albumin (BSA) adsorption assay revealed considerably lower protein adsorption of P1-P5 than PEI; P1 showed better DNA protection ability from degradation by DNase I than PEI; flow cytometry results suggested that any concentration of serum may not decrease the cellular uptake of P1/DNA polyplex; and confocal laser scanning microscopy also found that serum has little effect on the transfection. By using specific cellular uptake inhibitors, we found that the polyplexes enter the cells mainly via caveolae and microtubule-mediated pathways. We believe that this ring-opening polymerization may be an effective synthetic approach toward gene delivery materials with high biological activity.
authors.affiliation: Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, Sichuan University , Chengdu 610064, People's Republic of China.
authors.forename: Qin-Fang
authors.initials: QF
authors.lastname: Zhang
authors.forename: Qing-Ying
authors.initials: QY
authors.lastname: Yu
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Geng
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
authors.forename: Wan-Xia
authors.initials: WX
authors.lastname: Wu
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Gu
authors.forename: Xiao-Qi
authors.initials: XQ
authors.lastname: Yu
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D005822:Genetic Vectors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D011073:Polyamines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D000071228:Polyelectrolytes; D058105:Polymerization; D012710:Serum Albumin, Bovine; D014162:Transfection / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D011073:Polyamines; D000071228:Polyelectrolytes; D012710:Serum Albumin, Bovine
keywords: cationic polymer; cellular uptake; nonviral gene vector; ring-opening polymerization; serum tolerance