Biomimetic nanoparticles co-deliver hirudin and lumbrukinase to ameliorate thrombus and inflammation for atherosclerosis therapy.

Atherosclerosis (AS) is a progressive inflammatory disease, and thrombosis most likely leads to cardiovascular morbidity and mortality globally. Thrombolytic drugs alone cannot completely prevent thrombotic events, and treatments targeting thrombosis also need to regulate the inflammatory process. Based on the dynamic pathological development of AS, biomimetic thrombus-targeted nanoparticles HMTL@PM were prepared. Hirudin and lumbrukinase, effective substances of traditional Chinese medicine, were self-assembled under the action of tannic acid and Mn2+. HMTL@PM dissociated in the weakly acidic microenvironment of atherosclerosis and exhibited excellent therapeutic effects, including alleviating inflammation, dissolving thrombus, anticoagulation, and promoting cholesterol efflux. HMTL@PM effectively regulated the progression of AS and provided a new perspective for the development of drug delivery systems for AS therapy, which holds important research significance for reducing the mortality of cardiovascular and cerebrovascular diseases.