Induction of Angiogenesis by Controlled Delivery of Vascular Endothelial Growth Factor Using Nanoparticles

作者：Jiaqi Xie, Haibin Wang, Yunya Wang, Fangping Ren, Wei Yi, Kun Zhao, Zilin Li, Qiang Zhao, Zhenhua Liu, Hong Wu, Chunhu Gu, YI Ding-hua · 发表于：Cardiovascular Therapeutics · 年份：2012 · DOI：10.1111/j.1755-5922.2012.00317.x · 被引用次数：32 · 研究领域：Angiogenesis and VEGF in Cancer、Nanoparticle-Based Drug Delivery、Electrospun Nanofibers in Biomedical Applications

AIMS: The study reports the feasibility and efficiency of vascular endothelial growth factor (VEGF) delivery using nanoparticles synthesized from glycidyl methacrylated dextran (Dex-GMA) and gelatin for therapeutic angiogenesis. METHODS: The nanoparticles were prepared using phase separation method, and the drug release profile was determined by ELISA study. The bioactivity of VEGF-incorporated nanoparticles (VEGF-NPs) were determined using tube formation assay. A rabbit hind limb ischemia model was employed to evaluate the in vivo therapeutic effect. Blood perfusion was measured by single-photon emission computed tomography (SPECT). Vessel formation was evaluated by contrast angiography and immunohistochemistry. RESULTS: The nanoparticles synthesized were spherical in shape with evenly distributed size of about 130 ± 3.5 nm. The VEGF encapsulated was released in a biphase manner, with the majority of 69% released over 1-12 days. Tube formation assays showed increased tubular structures by VEGF-NP compared with empty nanoparticles and no treatment. Both free VEGF and VEGF-NP significantly increased blood perfusion compared with empty nanoparticles (both P < 0.001), but it was much higher in VEGF-NP-treated limbs (P < 0.001). Contrast angiography and immunohistological analysis also revealed more significant collateral artery formation and higher capillary density in VEGF-NP-treated limbs. CONCLUSIONS: Dex-GMA and gelatin-based nanoparticles could provide sustained release of ...