Park, Kyeongsoon Kim, Yoo-Shin Lee, Gee Young Park, Rang-Woon Kim, In-San Kim, Sang Yoon Byun, Youngro 2024-01-20T22:05:21Z 2024-01-20T22:05:21Z 2022-01-25 2008-12 0724-8741 https://pubs.kist.re.kr/handle/201004/132898 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. To evaluate antiangiogenic activity of cRGD-HL, we performed tests on endothelial cell adhesion and migration to vitronectin, tube formation, binding affinity to purified alpha(v)beta(3) 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. 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 alpha(v)beta(3) 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 alpha(v)beta(3)-mediated interaction, resulting in the enhanced antitumoral activity against SCC7 tumor. 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. English SPRINGER/PLENUM PUBLISHERS Tumor Endothelial Cell Targeted Cyclic RGD-modified Heparin Derivative: Inhibition of Angiogenesis and Tumor Growth Article 10.1007/s11095-008-9643-y 1 PHARMACEUTICAL RESEARCH, v.25, no.12, pp.2786 - 2798 PHARMACEUTICAL RESEARCH 25 12 2786 2798 N scie scopus 000261343500011 2-s2.0-57149126267 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article ANTITUMOR-ACTIVITY CANCER-THERAPY DRUG-DELIVERY GENE DELIVERY MOUSE MODEL PEPTIDES VITRONECTIN MICE NEOVASCULATURE PROLIFERATION angiogenesis heparin derivative lithocholic acid RGD SCC7