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

Abstract

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.