Thrombus targeting aspirin particles for near infrared imaging and on-demand therapy of thrombotic vascular diseases

A blood clot (thrombus)is formed as a final product of the hemostatic process with two major components, a mesh of cross-linked fibrin and platelets activated by high concentration of hydrogen peroxide (H₂O₂). Thrombus formation impedes blood flow to brain and heart and is a principle cause of life-threatening diseases such as stroke and myocardial infarction. Aspirin has been widely used for the treatment and prevention of various cardiovascular diseases, but is unable to target a thrombus and scavenge a high level of H₂O₂. In this study, we report thrombus targeting aspirin polyconjugate particles (T-APP)as a near infrared imaging agent and on-demand therapeutic agent for thrombotic vascular diseases. T-APP were formulated from H₂O₂-activatable aspirin polyconjugate, fibrin-specific peptides and fluorescent IR780. In mouse models of tail bleeding and arterial thrombosis, T-APP targeted the thrombosed vessels rapidly with excellent specificity. T-APP also exerted highly strong antithrombotic activity in the thrombosed vessel by suppressing anti-inflammatory cytokines and inhibiting platelet activation. Based on the unique features such as specific thrombus targeting, H₂O₂ scavenging, and on-demand therapeutic actions, the rationally engineered T-APP have important ramifications on imaging and on-demand therapy of thrombotic disorders.