Control of angiogenesis by VEGF and endostatin-encapsulated protein microcrystals and inhibition of tumor angiogenesis
Control of angiogenesis by VEGF and endostatin-encapsulated protein microcrystals and inhibition of tumor angiogenesis
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DOI：
10.1016/j.biomaterials.2013.10.051
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发表时间：
2014-01-01
期刊：
影响因子：
14
通讯作者：
Mori, Hajime
中科院分区：
文献类型：
--
作者：
Matsumoto, Goichi;Hirohata, Rie;Mori, Hajime
细胞因子在蛋白微晶（多面体）内的包封是一种很有前途的稳定和递送治疗蛋白的方法。在这里，我们研究血管内皮生长因子（VEGF）微晶体和内皮抑素微晶体对血管生成的影响。通过蛋白二硫键异构酶的过表达，成功地将VEGF包被在昆虫伪病毒微晶体中。我们观察到VEGF微晶体增加了p42/p44 MAP激酶的磷酸化，刺激了人脐静脉内皮细胞（HUVECs）的增殖、迁移和网络和管的形成。内皮抑素也被成功包裹成微晶体。内皮抑素微晶体具有抗血管生成活性，抑制HUVECs的迁移、网络和管状形成。局部给药小鼠内皮抑素微晶体抑制血管生成和肿瘤生长，在治疗组和对照组之间有明显的显著差异。内皮抑素微晶体仅影响血管生成，但与对照组相比，对淋巴管生成无显著影响。局部治疗使用内皮抑素微晶体提供了一种潜在的方法来实现抗血管生成分子的持续治疗释放，用于癌症治疗。(C) 2013 Elsevier Ltd.版权所有。
Encapsulation of cytokines within protein microcrystals (polyhedra) is a promising approach for the stabilization and delivery of therapeutic proteins. Here, we investigate the influence of vascular endothelial growth factor (VEGF) microcrystals and endostatin microcrystals on angiogenesis. VEGF was successfully encapsulated into microcrystals derived from insect cypovirus with overexpression of protein disulfide bond isomerase. VEGF microcrystals were observed to increase the phosphorylation of p42/p44 MAP kinase and to stimulate the proliferation, migration, and network and tube formation of human umbilical vein endothelial cells (HUVECs). Endostatin was also successfully encapsulated into microcrystals. Endostatin microcrystals showed antiangiogenesis activities and inhibited the migration, and network and tube formation of HUVECs. Local administration of endostatin microcrystals in mice inhibited both angiogenesis and tumor growth with clear significant differences between treatment and control groups. Endostatin microcrystals only affected angiogenesis, but had no significant effect on lymphangiogenesis compared to controls. Local therapy using endostatin microcrystals offers a potential approach to achieve sustained therapeutic release of antiangiogenic molecules for cancer treatment. (C) 2013 Elsevier Ltd. All rights reserved.