Biomimetic liposomes hybrid with platelet membranes for targeted therapy of atherosclerosis

Abstract

Atherosclerosis is the underlying cause of most cardiovascular events and responsible for almost one third of all deaths worldwide due to the lack of efficient strategies for targeted therapy. Platelets participate in pathological processes of atherosclerosis, and a variety of biomimetic nanoparticles have been developed for targeted drug delivery by mimicking the natural homing of platelets to disease sites. Inspired by the interaction of platelet membrane components with atherosclerosis plaques, we designed biomimetic liposomes composed of artificial liposomes hybrid with platelet membranes (P-Lipo) for atherosclerosis targeting. P-Lipo possessed the multivalent targeting properties inherited from platelet membranes and the advantages of artificial liposomes as drug carriers. In addition, P-Lipo displayed a 5.91-fold increase in accumulation into the atherosclerotic lesion in vivo, indicating its higher homing and deeper penetration into atherosclerosis plaques than conventional liposomes. Using an atheroprotective drug, rapamycin, as the model drug, P-Lipo most potently inhibited atherosclerosis development among all treatment groups while not causing systemic toxicity. Our results provide a platelet-mimetic platform with a high clinical translation potential for the treatment of atherosclerosis and other platelets-involved diseases.