title: Biodegradable poly(amine-co-ester) terpolymers for targeted gene delivery.
abstract: Many synthetic polycationic vectors for non-viral gene delivery show high efficiency in vitro, but their usually excessive charge density makes them toxic for in vivo applications. Here we describe the synthesis of a series of high molecular weight terpolymers with low charge density, and show that they exhibit efficient gene delivery, some surpassing the efficiency of the commercial transfection reagents Polyethylenimine and Lipofectamine 2000. The terpolymers were synthesized via enzyme-catalyzed copolymerization of lactone with dialkyl diester and amino diol, and their hydrophobicity adjusted by varying the lactone content and by selecting a lactone comonomer of specific ring size. Targeted delivery of the pro-apoptotic TRAIL gene to tumour xenografts by one of the terpolymers results in significant inhibition of tumour growth, with minimal toxicity both in vitro and in vivo. Our findings suggest that the gene delivery ability of the terpolymers stems from their high molecular weight and increased hydrophobicity, which compensates for their low charge density.
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, Connecticut 06511, USA.
authors.forename: Jiangbing
authors.initials: J
authors.lastname: Zhou
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Cheng
authors.forename: Toral R
authors.initials: TR
authors.lastname: Patel
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Weller
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Piepmeier
authors.forename: Zhaozhong
authors.initials: Z
authors.lastname: Jiang
authors.forename: W Mark
authors.initials: WM
authors.lastname: Saltzman
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D057809:HEK293 Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity; D009369:Neoplasms / Q000628:therapy; D011073:Polyamines / Q000737:chemistry* / Q000633:toxicity; D011108:Polymers / Q000737:chemistry* / Q000633:toxicity; D018675:Toxicity Tests
chemical_list: D011073:Polyamines; D011108:Polymers