Biomimetic Platelet Nanomotors for Site-Specific Thrombolysis and Ischemic Injury Alleviation

Due to the mortality associated with thrombosis and itshigh recurrencerate, there is a need to investigate antithrombotic approaches. Noninvasivesite-specific thrombolysis is a current approach being used; however,its usage is characterized by the following limitations: low targetingefficiency, poor ability to penetrate clots, rapid half-life, lackof vascular restoration mechanisms, and risk of thrombus recurrencethat is comparable to that of traditional pharmacological thrombolysisagents. Therefore, it is vital to develop an alternative techniquethat can overcome the aforementioned limitations. To this end, a cotton-ball-shapedplatelet (PLT)-mimetic self-assembly framework engineered with a phototherapeuticpoly(3,4-ethylenedioxythiophene) (PEDOT) platform has been developed.This platform is capable of delivering a synthetic peptide derivedfrom hirudin P6 (P6) to thrombus lesions, forming P6@PEDOT@PLT nanomotorsfor noninvasive site-specific thrombolysis, effective anticoagulation,and vascular restoration. Regulated by P-selectin mediation, the P6@PEDOT@PLTnanomotors target the thrombus site and subsequently rupture undernear-infrared (NIR) irradiation, achieving desirable sequential drugdelivery. Furthermore, the movement ability of the P6@PEDOT@PLT nanomotorsunder NIR irradiation enables effective penetration deep into thrombuslesions, enhancing bioavailability. Biodistribution analyses haveshown that the administered P6@PEDOT@PLT nanomotors exhibit extendedcirculation time and metabolic capabilities. In addition, the photothermaltherapy/photoelectric therapy combination can significantly augmentthe effectiveness (ca. 72%) of thrombolysis. Consequently, the preciselydelivered drug and the resultant phototherapeutic-driven heat-shockprotein, immunomodulatory, anti-inflammatory, and inhibitory plasminogenactivator inhibitor-1 (PAI-1) activities can restore vessels and effectivelyprevent rethrombosis. The described biomimetic P6@PEDOT@PLT nanomotorsrepresent a promising option for improving the efficacy of antithrombotictherapy in thrombus-related illnesses.