Peripheral artery disease is an atherosclerotic stenosis in the peripheral vasculature that is typically treated via percutaneous transluminal angioplasty. Deployment of the angioplasty balloon damages the endothelial layer， exposing the underlying collagen and allowing for the binding and activation of circulating platelets which initiate an inflammatory cascade leading to eventual restenosis. Here， we report on collagen-binding sulfated poly(N-isopropylacrylamide) nanoparticles that are able to target to the denuded endothelium. Once bound， these nanoparticles present a barrier that reduces cellular and platelet adhesion to the collagenous surface by 67% in whole blood and 59% in platelet-rich plasma under biologically relevant shear rates. In vitro studies indicate that the collagen-binding nanoparticles are able to load and release therapeutic quantities of anti-inflammatory peptides， with the particles reducing inflammation in endothelial and smooth muscle cells by 30% and 40% respectively. Once bound to collagen， the nanoparticles increased endothelial migration while avoiding uptake by smooth muscle cells， indicating that they may promote regeneration of the damaged endothelium while remaining anchored to the collagenous matrix and locally releasing anti-inflammatory peptides into the injured area. Combined， these collagen-binding nanoparticles have the potential to reduce inflammation， and the subsequent restenosis， while simultaneously promoting endothelial regeneration following balloon angioplasty.