20(S)-Ginsenoside-Rg3

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.