Ultrasound-responsive theranostic platform for real-time monitoring and efficient thrombolysis in tPA-resistant thrombi
There is no noninvasive solution for tPA-resistant thrombi while endovascular thrombectomy is the last option. Here, we proposed neutrophil extracellular traps (NETs), e-(?-glutamyl)lysine isopeptide bonds and fibrin scaffold as keychain in tPA-resistant thrombus, which was confirmed in the thrombi retrieved from stroke patients. A theranostic platform was designed for the combination of sonodynamic and mechanical thrombolysis under the guidance of ultrasonic imaging. Three rounds of 10 min noninvasive treatment led to the breakdown of the keychain, achieving great recanalization rate of 90% in rat occlusion model while tPA only made 10% improvement. RNA sequencing results and endothelium functional tests jointly indicated that the vascular homeostasis can be effectively reconstructed. The noninvasive theranostic capability presented in pig's lengthy thrombi (>8mm) and thrombosis-susceptible tissue engineered vascular grafts (TEVGs) indicated its clinical transformation prospects. Taken together, this non-invasive theranostic platform provides a new strategy for tPA-resistant thrombi. Overall design: Rat common carotid artery thrombosis was induced by ferric chloride, vascular recanalization was achieved under the combination of sonodynamic therapy and physical-explosion therapy, and the recanalized common carotid arteries were collected after one day and one week. Normal rat common carotid artery was taken as control.