title: Effective antitumor gene therapy delivered by polyethylenimine-conjugated stearic acid-g-chitosan oligosaccharide micelles.
abstract: Non-viral vesicle composing of low-molecular weight polyethylenimine-conjugated stearic acid-g-chitosan oligosaccharide (CSOSA-g-PEI) was synthesized for gene delivery and therapy. The synthesized CSOSA-g-PEI had good ion-buffer capabilities and DNA-binding capacity, which could form positively charged nano-sized particles (100-150 nm) with plasmid DNA; in vitro gene transfection tests demonstrated that CSOSA-g-PEI presented much lower cytotoxicity and corresponding transfection efficiency in comparison with Lipofectamine 2000 in both human cancer cells (Hela and MCF-7). The gene transfection of CSOSA-g-PEI/pDNA could be further enhanced in the presence of serum or by adding arginine during incubation of CSOSA-g-PEI micelles with plasmid DNA. The biodistribution experiments demonstrated CSOSA-g-PEI conjugate highly localized in the tumor tissue and indicated a persistently increased accumulation. In vivo antitumor activity results showed that CSOSA-g-PEI/plasmid pigment epithelium-derived factor formulation could effectively suppress the tumor growth (above 60% tumor inhibition) without systematic toxicity against animal body after intravenous injection.
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, PRC.
authors.forename: F-Q
authors.initials: FQ
authors.lastname: Hu
authors.forename: W-W
authors.initials: WW
authors.lastname: Chen
authors.forename: M-D
authors.initials: MD
authors.lastname: Zhao
authors.forename: H
authors.initials: H
authors.lastname: Yuan
authors.forename: Y-Z
authors.initials: YZ
authors.lastname: Du
mesh_terms: D000818:Animals; D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D004247:DNA / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy*; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D010957:Plasmids / Q000235:genetics; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D013229:Stearic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D008823:Micelles; D009844:Oligosaccharides; D013229:Stearic Acids; C031183:stearic acid; D011094:Polyethyleneimine; D004247:DNA; D048271:Chitosan