Von Willebrand Factor (VWF) Functionalized Nanoparticles for Targeting Athero-thrombotic Arteries

Atherosclerosis is a chronic inflammatory blood vessel disease characterized by atheromatous plaques deposition in arteries. Upon plaque fissuring or rupture at atherothrombotic sites, inner layers of the vessel wall are exposed, including collagen, which initiates an arterial thrombosis cascade - that can lead to lethal consequences. In arterial thrombosis, the glycoprotein Von Willebrand factor (VWF) plays a key role in recruiting platelets to sites of vascular injury under high shear stress conditions via its multiple domains. Inspired by the reciprocal interactions along the injury-VWF-platelet axis, we functionalized 200nm polystyrene nanoparticles with the VWF-A1 domain (VWF-A1 NPs), a domain which under high shear interacts with activated platelet, and studied their spatial adhesion to collagen or collagen-VWF coated, real-sized coronary stenosis models under physiological flow. When VWF-A1 NPs were perfused through a 75% stenosis model coated with collagen-VWF, the particles preferentially localized at the post stenotic region. When perfused through collagen-coated models or when the A1 coating density of nanoparticles was reduced by a 100-folds, the enhanced adhesion at the post-stenotic site was diminished. Our results indicate that VWF-A1 NPs exhibit a flow-structure dependent adhesion to VWF and illustrate the important role of studying cardiovascular nano-medicines in settings that closely model the size, geometry, and hemodynamics of pathological environments.