title: Dextranation of bioreducible cationic polyamide for systemic gene delivery.
abstract: A dextranated, bioreducible cationic polyamide was designed and employed for non-viral gene delivery in vitro and in vivo. Initially, a new bioreducible cationic polyamide with p-nitrophenyl ester terminal group (denoted as SSBAP) was synthesized by polycondensation reaction of an excess amount of bis-(p-nitrophenyl)-3, 3'-dithiodipropanoate and 1, 4-bis(3-aminopropyl)piperazine. The SSBAP was then chemically conjugated with 5 kDa amino-terminated dextran to yield dextran-SSBPA-dextran triblock copolymer (denoted as Dex-SSBAP-Dex). This copolymer was capable of binding genes to form nanoscale polyplexes with a near-neutral surface charge. Moreover, a sufficient gene release from the polyplexes in response to an intracellular reducing environment was observed. In vitro transfection against MCF-7 and SKOV-3 cells showed that Dex-SSBAP-Dex copolymer effectively transfected the cells with comparable efficiency to that of 2 5kDa branched or linear polyethylenimine as positive controls. Besides, intravenous administration of the copolymer-based polyplexes in nude mice afforded detectable gene expression largely in the lung. Importantly, the copolymer revealed low cytotoxicity in vitro, as determined by AlamarBlue assay, and caused no death of the mice. Dextranated, bioreducible cationic polyamide holds high potential as a non-viral vector for gene delivery.
authors.affiliation: The Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Tongji University, Shanghai, 200092, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Lin
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Song
authors.forename: Bo
authors.initials: B
authors.lastname: Lou
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
mesh_terms: D000818:Animals; D055592:Biophysical Phenomena; D002412:Cations; D045744:Cell Line, Tumor; D002470:Cell Survival; D003102:Colloids / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D061986:MCF-7 Cells; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009757:Nylons / Q000737:chemistry*; D010316:Particle Size; D004369:Pentetic Acid / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D013499:Surface Properties
chemical_list: D002412:Cations; D003102:Colloids; D004220:Disulfides; D009757:Nylons; D011108:Polymers; D004369:Pentetic Acid; D011094:Polyethyleneimine
keywords: Dextran; disulfide; gene delivery; in vivo; transfection