title: Enzyme-synthesized poly(amine-co-esters) as nonviral vectors for gene delivery.
abstract: A family of biodegradable poly(amine-co-esters) was synthesized in one step via enzymatic copolymerization of diesters with amino-substituted diols. Diesters of length C(4) -C(12) (i.e., from succinate to dodecanedioate) were successfully copolymerized with diethanolamines with either an alkyl (methyl, ethyl, n-butyl, t-butyl) or an aryl (phenyl) substituent on the nitrogen. Upon protonation at slightly acidic conditions, these poly(amine-co-esters) readily turned to cationic polyelectrolytes, which were capable of condensing with polyanionic DNA to form nanometer-sized polyplexes. In vitro screening with pLucDNA revealed that two of the copolymers, poly(N-methyldiethyleneamine sebacate) (PMSC) and poly(N-ethyldiethyleneamine sebacate) (PESC), possessed comparable or higher transfection efficiencies compared with Lipofectamine 2000. PMSC/pLucDNA and PESC/pLucDNA nanoparticles had desirable particle sizes (40-70 nm) for cellular uptake and were capable of functioning as proton sponges to facilitate endosomal escape after cellular uptake. These polyplex nanoparticles exhibited extremely low cytotoxicity. Furthermore, in vivo gene transfection experiments revealed that PMSC is a substantially more effective gene carrier than PEI in delivering pLucDNA to cells in tumors in mice. All these properties suggest that poly(amine-co-esters) are promising nonviral vectors for safe and efficient DNA delivery in gene therapy.
authors.affiliation: School of Life Science and Technology, Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Zhaozhong
authors.initials: Z
authors.lastname: Jiang
authors.forename: Jiangbing
authors.initials: J
authors.lastname: Zhou
authors.forename: Shengmin
authors.initials: S
authors.lastname: Zhang
authors.forename: W Mark
authors.initials: WM
authors.lastname: Saltzman
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000648:ultrastructure; D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008049:Lipase / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D010957:Plasmids / Q000235:genetics; D011073:Polyamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014162:Transfection; D014780:Viruses / Q000235:genetics
chemical_list: D004952:Esters; D011073:Polyamines; D049452:Green Fluorescent Proteins; D004247:DNA; D008156:Luciferases; D008049:Lipase