Functionalization of Small Rigid Platforms with Cyclic RGD Peptides for Targeting Tumors Overexpressing αvβ3-Integrins

Gadolinium based Small Rigid Plaforms (SRPs) have previously demonstrated their efficiency for multimodal imaging and radiosensitization. Since the RGD sequence is well-known to be highly selective for alpha(v)beta(3) integrins, a cyclic pentapeptide containing the RGD motif (cRGDfK) has been grafted onto the SRP surface. An appropriate protocol led to the grafting of two targeting ligands per nano-object. The resulting nanoparticles have demonstrated a strong association with alpha(v)beta(3) integrins in comparison with cRADfK grafted SRPs as negative control. Flow cytometry and fluorescence microscopy have also been used to highlight the ability of the nanoparticles to target efficiently HEK293(beta 3) and U87MG cells. Finally the grafted radiosensitizing nanoparticles were intravenously injected into Nude mice bearing subcutaneous U87MG tumors and the signal observed by optical imaging was twice as high for SRP-cRGDfK compared to their negative analogue.