Département de chimie moléculaire

The $\alpha$v$\beta$3 and $\alpha$v$\beta$5 integrins, transmembrane glycoprotein receptors, are over-expressed in numerous tumors and in endothelial cells that constitute tumor blood vessels. As this protein selectively binds to the Arg-Gly-Asp (RGD) sequence contg. peptides, it is an attractive way to target tumors. Herein we have developed novel formulations for integrin mediated selective gene delivery. These formulations are composed of a novel palmitoylated tetrameric RGD contg. scaffold (named RAFT-RGD), cationic gemini cholesterol (GL5) and a natural helper lipid 1,2-dioleoyl-L-$\alpha$-glycero-3-phosphatidylethanolamine (DOPE). We have optimized a co-liposomal formulation to introduce the multivalent RGD-contg. macromol. in GL5: DOPE (GL5D) mixt. to produce GL5D-RGD. We have unambiguously shown the selectivity of these formulations towards cancer cells that over express $\alpha$v$\beta$3 and $\alpha$v$\beta$5 integrins. Two reporter plasmids, pEGFP-C3 and PGL-3, were employed for the transfection expts. and it was shown that GL5D-RGD liposomes increased exclusively the transfection in $\alpha$v$\beta$3 and $\alpha$v$\beta$5-overexpressing HeLa cells. [on SciFinder(R)]