The relationship between the cyclic-RGDfK ligand and αvβ3 integrin receptor

Ever since the finding that alpha v beta 3 integrin receptors are over expressed on the endothelial cell surfaces of tumor vasculatures relative to normal resting vasculatures was disclosed in 1994, alpha v beta 3 integrin receptor selective systems are finding increasing applications both for targeting anti-cancer drugs/genes selectively to tumor vasculatures and for imaging growing tumors. Among the cyclic peptide based integrin antagonists identified through both phage display and structure-activity studies, mainly alpha v beta 3 integrin selective cyclic peptide c(RGDfK-) has found most widespread exploitations for targeting chemotherapeutic drugs/genes to both tumor and tumor vasculatures in anti-angiogenic cancer therapy. Herein we show that a lipopeptide containing widely acclaimed alpha v beta 3 integrin receptor selective cyclic RGDfK ligand in its head-group area can effectively deliver genes into both the endothelial and tumor cells via all the three widely used integrin receptors namely alpha v beta 3, alpha v beta 5 & alpha 5 beta 1 integrins. We demonstrate that intravenous administration of the electrostatic complex of the cationic liposomes of an amphiphiles with cyclic RGDfK head-group and the anti-cancer p53 gene leads to significant tumor growth inhibition in a syngeneic mouse tumor model presumably through inducing apoptosis of tumor neovasculatures. The findings delineated herein provide experimental evidence that cyclic-RGDfK-ligand may not be that highly selective for alpha v beta 3 integrin receptor as is popularly believed. (C) 2013 Elsevier Ltd. All rights reserved.