In Vivo Phage Display Selection Yields Atherosclerotic Plaque Targeted Peptides for Imaging

Abstract

Atherosclerosis is a leading cause of morbidity and mortality in the Western world, yet specific imaging agents to detect and map inflammatory plaques are still lacking. We used in vivo phage display to interrogate early atherosclerotic lesions present in ApoE-/- mice with the goal of identifying plaque-associated endothelial cell internalized affinity ligands. We identified 30 phage families with some of these families exhibiting homology to known atherosclerotic proteins, namely, leukemia inhibitory factor, transferrin, and VLA-4. VLA-4 homologous peptides [termed vascular cellular adhesion molecule-1 (VCAM-1) internalizing peptide-28 (VINP28)] bound to and were internalized by VCAM-1-expressing cells and were inhibited by soluble VCAM-1. In addition, a VINP28 modified multimodal nanoparticle showed high affinity for endothelial cells expressing VCAM-1 but low affinity for macrophages or smooth muscle cells. The identified peptides represent a set of probes to interrogate the cell surface repertoire and potentially allow early detection of atherosclerosis.