In atherosclerosis, fatty plaques build up in the arteries. It is therefore common that people with cardiovascular disease at risk for atherosclerosis will take statins, or lipid-lowering drugs. However, a complementary approach may be to resolve the ongoing, chronic inflammation in atherosclerosis. Small fragment encapsulated of annexin A1 - a protein that promotes the resolution of inflammation in a polymeric nanoparticle and decorated the nanoparticle with a collagen IV-binding peptide, to target the therapeutic package to advanced atherosclerotic plaques. The Ac2-26 nanoparticles accumulated at vessel lesions in a mouse model of advanced atherosclerosis such as translational medicine. Once in place, the particles slowly released Ac2-26, which bound to immune cells, reducing oxidative stress, promoting collagen buildup and increasing the anti-inflammatory cytokine interleukin-10 in sum, working to resolve inflammation and stabilize the plaque. This new proresolving nanomedicine approach will need to be tested in larger vessels and in animal models more similar to human atherosclerosis. But this targeted therapy is a first of its kind, paving the way for a new type of therapy to prevent heart disease.