Platelet-targeted microbubbles inhibit re-occlusion after thrombolysis with transcutaneous ultrasound and microbubbles

Microbubbles (MBs) can augment the acoustic cavitation’ (US), thereby facilitating the thrombolysis of external ultrasound. But we observed re-thrombosis after successful thrombolysis by MBs and transcutaneous ultrasound in an endothelium injury model. This study was designed to explore whether platelet-targeted MBs can prevent the reformation of thrombi. Arterial injury was induced in canine femoral arteries with balloon, and the arteries were completely thrombotically occluded. The arteries were treated with intra-arterial MBs or platelet-targeted MBs (TMB) and transcutaneous low frequency ultrasound (LFUS) to achieve complete thrombolysis. The arterial flow was monitored with angiogram for 4 h following treatment. Results showed that both MBs and TMBs produced successful dissolution of clots in the presence of ultrasound. The re-occlusion began to occur 1 h after thrombolysis in MB/LFUS treatment, and 7 of 8 arteries were re-occluded within 3 h. Most of the arteries (7 of 8) in the TMB/LFUS group remained patent for 4 h following treatment. The flow tended to decrease after thrombolysis in MB/LFUS treatment. These results indicated that platelet-targeted microbubbles were beneficial in preventing re-thrombosis in vivo and microbubbles served as good carrier of thrombolytic and anticoagulation drugs.