VCAM‐1‐Targeted Gene Delivery Nanoparticles Localize to Inflamed Endothelial Cells and Atherosclerotic Plaques

The ability to target nanoparticles to the dysfunctional endothelium may present a new and innovative therapy for cardiovascular disease. In this work, an anti‐inflammatory gene therapy nanoparticle targeted to VCAM‐1, a protein overexpressed by inflamed endothelial cells located within atherosclerotic plaque, is developed. Targeting is accomplished via a peptide‐grafted coating for the nanoparticles. Nanoparticle binding to VCAM‐1 is probed via surface plasmon resonance with imaging to determine kinetics and binding dynamics. Targeted nanoparticles are internalized by transfected inflamed primary endothelial cells more than nontargeted controls (80% vs 30% positive cells) under both static and dynamic flow conditions. The nanoparticles also bind specifically to VCAM‐1+ endothelial cells within atherosclerotic plaque from mouse models in both the aortic sinus and whole aorta. Taken together, this nanoparticle formulation may be an effective and specific strategy for anti‐inflammatory therapy within the context of atherosclerosis. In this work, gene delivery nanoparticles are targeted to VCAM‐1 using a peptide‐grafted PEGylated coating. The coated nanoparticles are able to specifically bind VCAM‐1 at the protein, cellular, and tissue level while maintaining their gene transfection capabilities.