Nano sphere-mediated deliver of vascular endothelial growth factor gene for therapeutic angiogenesis in mouse ischemic limbs
Nano sphere-mediated deliver of vascular endothelial growth factor gene for therapeutic angiogenesis in mouse ischemic limbs
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DOI：
10.1016/j.biomaterials.2007.11.004
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发表时间：
2008-03-01
期刊：
影响因子：
14
通讯作者：
Kim, Byung-Soo
中科院分区：
文献类型：
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作者：
Kang, Sun-Woong;Lim, Hee-Won;Kim, Byung-Soo
聚合物纳米球介导的基因递送可以维持质粒DNA（pDNA）施用的持续时间。在这项研究中，聚（乳酸-共-乙醇酸）（PLGA）纳米球作为基因载体进行了评估。负载pDNA的PLGA纳米球以高包封率（87%）配制。纳米球持续释放pDNA 11天。释放的pDNA保持其结构和功能完整性。此外，PLGA纳米球在体外和体内显示出比聚乙烯亚胺（PEI）更低的细胞毒性。将携带血管内皮生长因子（VEGF）基因的PLGA纳米球注射到缺血肢体模型的骨骼肌中，并与PEI/pDNA或裸pDNA在体内的基因表达进行比较。在给药后12天，PLGA纳米球/pDNA与PEI/pDNA和裸pDNA相比具有显著更高的VEGF表达水平。此外，使用PLGA纳米球的基因治疗在缺血部位比裸pDNA和PEI/pDNA导致更广泛的新血管形成。这些结果表明，PLGA纳米球可能是一个潜在的载体，骨骼肌基因传递应用。(c)2007爱思唯尔有限公司保留所有权利。
Polymeric nanosphere-mediated gene delivery may sustain the duration of plasmid DNA (pDNA) administration. In this study, poly(lactic-co-glycolic acid) (PLGA) nanospheres were evaluated as a gene carrier. The pDNA-loaded PLGA nanospheres were formulated with high encapsulation efficiency (87%). The nanospheres sustained release of pDNA for I I days. The released pDNA maintained its structural and functional integrity. Furthermore, the PLGA nanospheres showed lower cytotoxicity than polyethylenimine (PEI) in vitro and in vivo. The nanospheres with vascular endothelial growth factor (VEGF) gene were injected into skeletal muscle of ischemic limb model, and gene expression mediated by the PLGA nanospheres with VEGF gene was compared to that of PEI/pDNA or naked pDNA in vivo. PLGA nanosphere/pDNA had significantly higher VEGF expression levels in comparison to PEI/pDNA and naked pDNA at 12 days after administration. In addition, gene therapy using PLGA nanospheres resulted in more extensive neovascularization at ischemic sites than both naked pDNA and PEI/pDNA. These results indicated that PLGA nanosphere might be useful as a potential carrier for skeletal muscle gene delivery applications. (c) 2007 Elsevier Ltd. All rights reserved.