Abstract
Cell‐selective delivery using ligand‐decorated nanoparticles is a promising modality for treating cancer and vascular diseases. We are developing liposome nanoparticles surface‐modified by RGD peptide ligands having targeting specificity to integrin GPIIb‐IIIa. This integrin is upregulated and stimulated into a ligand‐binding conformation on the surface activated platelets. Activated‐platelet adhesion and aggregation are primary events in atherosclerosois, thrombosis, and restenosis. Hence, platelet‐targeted nanoparticles hold the promise of vascular site‐selective delivery of drugs and imaging probes. Here, we report in vitro and ex vivo microscopy studies of platelet‐targeting by liposomes surface‐modified with a cyclic RGD peptide. The peptide‐modified liposomes were labeled either with a lipophilic fluorophore or with lipid‐tethered Nanogold®. For in vitro tests, coverslip‐adhered activated human platelets were incubated with probe‐labeled liposomes, followed by analysis with fluorescence microscopy, phase contrast microscopy, and scanning electron microscopy (SEM). For in vivo tests, the liposomes were introduced within a catheter‐injured carotid artery restenosis model in rats and post‐euthanasia, the artery was imaged ex vivo by fluorescence microscopy and SEM. All microscopy results showed successful platelet‐targeting by the peptide‐modified liposomes. The in vitro SEM results also enabled visualization of nanoscopic liposomes attached to activated platelets. The results validate our nanoparticle design for site‐selective vascular delivery. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010