Control of angiogenesis by VEGF and endostatin-encapsulated protein microcrystals and inhibition of tumor angiogenesis

Goichi Matsumoto, Rie Hirohata, Kousuke Hayashi, Yoko Sugimoto, Eiji Kotani, Junji Shimabukuro, Tomoko Hirano, Yumiko Nakajima, Shin Kawamata, Hajime Mori

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15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1326-1333
Number of pages8
JournalBiomaterials
Volume35
Issue number4
DOIs
Publication statusPublished - Jan 2014

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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    Matsumoto, G., Hirohata, R., Hayashi, K., Sugimoto, Y., Kotani, E., Shimabukuro, J., Hirano, T., Nakajima, Y., Kawamata, S., & Mori, H. (2014). Control of angiogenesis by VEGF and endostatin-encapsulated protein microcrystals and inhibition of tumor angiogenesis. Biomaterials, 35(4), 1326-1333. https://doi.org/10.1016/j.biomaterials.2013.10.051