title: Novel hyperbranched polyamidoamine nanoparticles for transfecting skeletal myoblasts with vascular endothelial growth factor gene for cardiac repair.
abstract: We investigated the feasibility and efficacy of hyperbranched polyamidoamine (hPAMAM) mediated human vascular endothelial growth factor-165 (hVEGF(165)) gene transfer into skeletal myoblasts for cardiac repair. The hPAMAM was synthesized using a modified one-pot method. Encapsulated DNA was protected by hPAMAM from degradation for over 120 min. The transfection efficiency of hPAMAM in myoblasts was 82.6 ± 7.0% with cell viability of 94.6 ± 1.4% under optimal conditions. The hPAMAM showed much higher transfection efficiency (P < 0.05) than polyetherimide and Lipofectamine 2000 with low cytotoxicity. The transfected skeletal myoblasts gave stable hVEGF(165) expression for 18 days. After transplantation of hPAMAM-hVEGF(165) transfected cells, apoptotic myocardial cells decreased at day 1 and heart function improved at day 28, with increased neovascularization (P < 0.05). These results indicate that hPAMAM-based gene delivery into myoblasts is feasible and effective and may serve as a novel and promising non-viral DNA vehicle for gene therapy in myocardial infarction.
authors.affiliation: Department of Cardiac Surgery, Zhongshan Hospital, Fudan University & Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhu
authors.forename: Changfa
authors.initials: C
authors.lastname: Guo
authors.forename: Hao
authors.initials: H
authors.lastname: Lai
authors.forename: Wuli
authors.initials: W
authors.lastname: Yang
authors.forename: Yu
authors.initials: Y
authors.lastname: Xia
authors.forename: Dong
authors.initials: D
authors.lastname: Zhao
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods; D006331:Heart Diseases / Q000628:therapy*; D051379:Mice; D032448:Myoblasts, Skeletal / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D011073:Polyamines / Q000737:chemistry*; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism*
chemical_list: C531249:Poly(amidoamine); D011073:Polyamines; D042461:Vascular Endothelial Growth Factor A