Control of angiogenesis by VEGF and endostatin-encapsulated protein microcrystals and inhibition of tumor angiogenesis
| Autor: | Shin Kawamata, Kousuke Hayashi, Junji Shimabukuro, Hajime Mori, Goichi Matsumoto, Tomoko Hirano, Yoko Sugimoto, Rie Hirohata, Yumiko Nakajima, Eiji Kotani |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Vascular Endothelial Growth Factor A
Materials science Angiogenesis Biophysics Neovascularization Physiologic Bioengineering macromolecular substances Umbilical vein Biomaterials chemistry.chemical_compound Mice Cell Movement Cell Line Tumor Neoplasms Human Umbilical Vein Endothelial Cells Animals Humans Cell Proliferation Tube formation Drug Carriers Neovascularization Pathologic Cell growth Lymphangiogenesis Endostatins Vascular endothelial growth factor Vascular endothelial growth factor A chemistry Mechanics of Materials Immunology cardiovascular system Ceramics and Composites Cancer research Endostatin Crystallization |
| Zdroj: | Biomaterials. 35(4) |
| ISSN: | 1878-5905 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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