Targeting Nanomotor with Near-Infrared/Ultrasound Triggered-Transformation for Polystage-Propelled Cascade Thrombolysis and Multimodal Imaging Diagnosis

Nowadays, cardiovascular and cerebrovascular diseases caused by venous thromboembolism become main causes of mortality around the world. The current thrombolytic strategies in clinics are confined primarily due to poor penetration of nanoplatforms, limited thrombolytic efficiency, and extremely-low imaging accuracy. Herein, a novel nanomotor (NM) is engineered by combining iron oxide/perfluorohexane (PFH)/urokinase (UK) into liposome nanovesicle, which exhibits near-infrared/ultrasound (NIR/US) triggered transformation, achieves non-invasive vein thrombolysis, and realizes multimodal imaging diagnosis altogether. Interestingly, a three-step propelled cascade thrombolytic therapy is revealed from such intelligent NM. First, the NM is effectively herded at the thrombus site under guidance of a magnetic field. Afterwards, stimulations of NIR/US propel phase transition of PFH, which intensifies penetration of the NM toward deep thrombus dependent on cavitation effect. Ultimately, UK is released from the collapsed NM and achieves pharmaceutical thrombolysis in a synergistic way. After an intravenous injection of NM in vivo, the whole thrombolytic process is monitored in real-time through multimodal photoacoustic, ultrasonic, and color Doppler ultrasonic imagings. Overall, such advanced nanoplatform provides a brand-new strategy for time-critical vein thrombolytic therapy through efficient thrombolysis and multimodal imaging diagnosis. A kind of iron oxide/perfluorohexane/urokinase-based liposome nanomotor with near-infrared/ultrasound triggered transformation ability is elaborately-engineered for achieving relatively non-invasive vein thrombolysis and multimodal imaging diagnosis. Such polystage-propelled thrombolytic cascade strategy greatly improves thrombolytic efficiency through magnetic field navigation, cavitation effect of perfluorohexane phase transition, and synergistic hyperthermia or pharmaceutical thrombolysis, presenting excellent prospects of clinical translations for time-critical vein thrombolytic therapy.image