Novel hyperbranched polyamidoamine nanoparticles for transfecting skeletal myoblasts with vascular endothelial growth factor gene for cardiac repair

Novel hyperbranched polyamidoamine nanoparticles for transfecting skeletal myoblasts with vascular endothelial growth factor gene for cardiac repair
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新型超支化聚酰胺胺纳米粒子,用于用血管内皮生长因子基因转染骨骼肌细胞,用于心脏修复

DOI:
10.1007/s10856-011-4424-2
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发表时间:
2011-08
期刊:
Journal of Materials Science: Materials in Medicine
影响因子:
--
通讯作者:
Wang, Chunsheng
Wang, Chunsheng
中科院分区:
其他
文献类型:
--
作者:
Zhu, Kai;Guo, Changfa;Lai, Hao;Yang, Wuli;Xia, Yu;Zhao, Dong;Wang, Chunsheng

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我们研究了超支化聚酰胺胺(hPAMAM)介导的人血管内皮生长因子165(hVEGF 165)基因转染骨骼肌成肌细胞用于心脏修复的可行性和有效性。使用改进的一锅法合成hPAMAM。通过hPAMAM保护包封的DNA免于降解超过120分钟。在优化条件下,hPAMAM转染成肌细胞的效率为82.6 ± 7.0%,细胞存活率为94.6 ± 1.4%。hPAMAM的转染效率明显高于聚醚酰亚胺和Lipofectamine 2000(P< 0.05),且细胞毒性较低。转染的骨骼肌成肌细胞在18天内稳定表达hVEGF 165。转染hPAMAM-hVEGF 165的细胞移植后第1天心肌细胞凋亡减少,第28天心功能改善,新生血管增多(P< 0.05)。这些结果表明,hPAMAM为基础的基因导入成肌细胞是可行的和有效的,并可能作为一个新的和有前途的非病毒DNA载体的基因治疗心肌梗死。
We investigated the feasibility and efficacy of hyperbranched polyamidoamine (hPAMAM) mediated human vascular endothelial growth factor-165 (hVEGF165) 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 hVEGF165expression for 18 days. After transplantation of hPAMAM–hVEGF165transfected 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.
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