Cyclic RGDyk-conjugated LMWH-taurocholate derivative as a targeting angiogenesis inhibitor.

Abstract

LMWH-taurocholate derivative (LHT7) has been reported as a novel angiogenesis inhibitor, due to its ability to bind to several kinds of growth factors, which play critical roles in tumor angiogenesis. In this study, we have highlighted the enhanced antiangiogenic activity of LHT7, by using cyclic RGDyk (cRGD), a targeting moiety that was chemically conjugated to LHT7 via amide bond. The SPR study revealed that cRGD-LHT7 bound to α(v)β(3) integrin as strongly as cRGD, and it bound to VEGF as strongly as LHT7. Importantly, in vitro anti-angiogenesis studies revealed that cRGD-LHT7 had a significant inhibition effect on HUVEC tubular formation. Finally, cRGD-LHT7 showed a greater inhibitory efficiency on the tumor growth in the U87MG xenograft model than the original LHT7, which was owed to its ability to target the tumor cells. All of these findings demonstrated that cRGD-LHT7 targeted α(v)β(3) integrin-positive cancer cells and endothelial cells, resulting in a greater anti-angiogenesis effect on the solid tumors.

• Authors: Asarasin Adulnirath, Seung Woo Chung, Jooho Park, Seung Rim Hwang, Ji-Young Kim, Victor C Yang, Sang Yoon Kim, Hyun Tae Moon, Youngro Byun
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 164 Issue 1 Pg. 8-16 (Nov 28 2012) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 23063549 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• Heparin, Low-Molecular-Weight
• Integrin alphaVbeta3
• LHT7 compound
• Peptides, Cyclic
• cRGD-LHT7
• cyclic arginine-glycine-aspartic acid peptide
• Taurocholic Acid

Topics

• Angiogenesis Inhibitors (chemical synthesis, chemistry, pharmacology, therapeutic use)
• Animals
• Cell Line, Tumor
• Cell Survival (drug effects)
• Heparin, Low-Molecular-Weight (analogs & derivatives, chemical synthesis, chemistry, pharmacology, therapeutic use)
• Human Umbilical Vein Endothelial Cells
• Humans
• Integrin alphaVbeta3 (metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Microscopy, Confocal
• Microtubules (drug effects, ultrastructure)
• Molecular Structure
• Peptides, Cyclic (chemistry)
• Protein Binding
• Taurocholic Acid (analogs & derivatives, chemical synthesis, chemistry, pharmacology, therapeutic use)
• Xenograft Model Antitumor Assays