A functional antiplatelet nanomotor for tri-modal ablation of acute arterial thrombus.

Abstract

Timely and safe thrombolysis is a priority in the clinical management of acute arterial embolism. However, current drug therapies face the challenge of balancing therapeutic benefits with bleeding risks. Nanomotors emerge as a promising nonpharmaceutical modality for embolism recanalization, yet transient physical-force-driven antithrombotic therapy cannot achieve long-acting treatment, resulting in unsatisfactory therapeutic outcomes. Here, we exploit a functional antiplatelet nanomotor, which is precisely assembled from a photothermal photosensitizer (DiR), a photothermal-activatable nitric oxide (NO) donor (BNN6), and an antiplatelet drug (ticagrelor [TGL]). Under laser irradiation, the nanomotor achieves deep thrombus penetration through vigorous propulsion enabled by efficient NO generation, while on-site TGL release acts synergistically with NO to enhance antiplatelet function. As expected, the clot-piercing antiplatelet nanomotor displays striking thrombolytic effects in two artery embolism rat models. This study advances a photothermal/mechanical/antiplatelet tri-modal thrombolytic modality toward clinical applicability.