Biomimetic platelet membrane liposomes enable targeted shikonin delivery for thrombosis therapy

Thrombosis is central to cardiovascular disease, yet current therapies are limited by inefficient drug delivery, poor thrombus targeting, and bleeding risk. Here we present a biomimetic platelet membrane-coated liposomal nanoplatform (SK-PLT) that integrates natural pharmacologic activity with targeted delivery. In a high-throughput screen of 171 natural products, shikonin (SK) inhibited platelet aggregation induced by ADP, thrombin, and collagen, with inhibition rates of 83.3%, 73.5%, and 81.6%, respectively. SK was then loaded into liposomes formulated with ginsenoside Rg3, which provides intrinsic antiplatelet activity and improves liposomal stability. The platelet membrane coating preserved key adhesion receptors and endowed SK-PLT with high affinity for activated platelets and thrombi. In vitro, SK-PLT nearly abolished aggregation, adhesion, spreading, and clot retraction, and showed good hemocompatibility. In mouse models of carotid arterial thrombosis and deep vein thrombosis, SK-PLT accumulated at thrombi, decreased carotid vessel occlusion from 91.7% to 13.3%, and reduced venous thrombus weight from 37.6 mg to 19.2 mg, leading to recovery of local blood flow. Overall antithrombotic efficacy was comparable to ticagrelor, but SK-PLT caused less prolongation of bleeding time and lower systemic toxicity. This combination of pharmacologic activity and biomimetic targeting supports SK-PLT as a precise antithrombotic strategy with translational potential.