Nano sphere-mediated deliver of vascular endothelial growth factor gene for therapeutic angiogenesis in mouse ischemic limbs

被引:60
作者
Kang, Sun-Woong [2 ]
Lim, Hee-Won [2 ]
Seo, Sang-Woo [2 ,3 ]
Jeon, Oju [2 ]
Lee, Minhyung [1 ]
Kim, Byung-Soo [1 ]
机构
[1] Hanyang Univ, Dept Bioengn, Seoul 133791, South Korea
[2] Hanyang Univ, Dept Chem Engn, Seoul 133791, South Korea
[3] Seoul Natl Univ, Interdisciplinary Program Biomchem Engn & Biotech, Seoul 151744, South Korea
关键词
angiogenesis; gene therapy; nanoparticle; poly(lactic-co-glycolic acid);
D O I
10.1016/j.biomaterials.2007.11.004
中图分类号
R318 [生物医学工程];
学科分类号
0831 [生物医学工程];
摘要
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.
引用
收藏
页码:1109 / 1117
页数:9
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