Tumor endothelial cell targeted cyclic RGD-modified heparin derivative: Inhibition of angiogenesis and tumor growth

Kyeongsoon Park, Yoo Shin Kim, Gee Young Lee, Rang Woon Park, In San Kim, Sang Yoon Kim, Youngro Byun

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Purpose. We prepared tumor endothelium targeted cRGD-modified heparin derivative (cRGD-HL) by coupling heparin-lithocholic acid (HL) with cRGDyK, and evaluated inhibition effects of cRGD-HL on angiogenesis and tumor growth. Methods. To evaluate antiangiogenic activity of cRGD-HL, we performed tests on endothelial cell adhesion and migration to vitronectin, tube formation, binding affinity to purified αvβ3 integrin, and in vivo Matrigel plug assay. The antitumor activity of cRGD-HL was also evaluated by monitoring tumor growth and microvessel formation in squamous cell carcinoma (SCC7) tumor. Results. The cRGD-HL significantly inhibited adhesion and migration of endothelial cells to vitronectin, and tubular structures of endothelial cells. Compared to cRGDyK and HL, cRGD-HL has high binding affinity to purified αvβ3 integrin. The enhanced antiangiogenic effect of cRGD-HL was confirmed in Matrigel assay by showing the significant inhibition of bFGF-driven angiogenesis and blood vessel formation. It was thought that potent antiangiogenic effect of cRGD-HL was probably due to the interference of αvβ3-mediated interaction, resulting in the enhanced antitumoral activity against SCC7 tumor. Conclusion. These results demonstrated that cRGD-modified heparin derivative enhanced anti-angiotherapeutic effects against solid tumor, and therefore, it could be applied to treat various cancers and angiogenic diseases as a potent angiogenesis inhibitor.

Original languageEnglish
Pages (from-to)2786-2798
Number of pages13
JournalPharmaceutical research
Volume25
Issue number12
DOIs
Publication statusPublished - 2008 Dec

Keywords

  • Angiogenesis
  • Heparin derivative
  • Lithocholic acid
  • RGD
  • SCC7

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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