The increased expression of VCAM-1 at sites of atherogenesis provides a potential target for the selective delivery of drug carriers to sites of atherosclerosis. In this study, we conjugated a VCAM-1 mAb to polystyrene particles and particles made from the biodegradable polymer poly(sebacic acid)-block-polyethylene glycol (PSA-PEG). Protein detection assays (flow cytometry and ELISA) revealed a significant level of VCAM-1 mAb conjugated to the polystyrene and PSA-PEG particles. We investigated the adhesion of the resulting α-VCAM-1 particles to arterial endothelium in a murine model of atherosclerosis (the ApoE^-/- mouse). We found that α-VCAM-1 particles exhibit significantly higher adhesion compared to IgG particles. The ratio of α-VCAM-1 particle adhesion to IgG particle adhesion (ligand efficiency), ranged from ~8 to ~32 depending on the polymer used to make up the particles and the artery observed. The ratio of the number of particles adherent in the ApoE^-/- mice to the number adherent in the wild type mice (selectivity), was between 1.2 and 1.9 for the polystyrene particles and ~5 for the PSA-PEG particles. Within the ApoE^-/- mice, we observed ~2.5 times higher adhesion of the α-VCAM-1 particles to overt plaque regions compared to non-plaque regions of the aorta. These results strongly suggest that drug carriers conjugated with ligands for VCAM-1 will selectively and avidly bind to sites of atherosclerosis via the increased expression of VCAM-1.

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