Ever since the finding that αvβ3
integrin receptors are over expressed on the endothelial cell surfaces of
tumor vasculatures relative to normal resting vasculatures was disclosed in 1994, αvβ3
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 αvβ3
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 αvβ3
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 αvβ3, αvβ5 & α5β1
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 αvβ3
integrin receptor as is popularly believed.