Ultrasound Trigger Ce-Based MOF Nanoenzyme For Efficient Thrombolytic Therapy

The inflammatory damage caused by thrombus formation and dissolution can increase the risk of thrombotic complications on top of cell death and organ dysfunction caused by thrombus itself. Therefore, a rapid and precise thrombolytic therapy strategy is in urgent need to effectively dissolve thrombus and resist oxidation simultaneously. In this study, Ce-UiO-66, a cerium-based metal-organic framework (Ce-MOF) with reactive oxygen species (ROS) scavenging properties, encapsulated by low-immunogenic mesenchymal stem cell membrane with inflammation-targeting properties, is used to construct a targeted nanomedicine Ce-UiO-CM. Ce-UiO-CM is applied in combination with external ultrasound stimulation for thrombolytic therapy in rat femoral artery. Ce-UiO-66 has abundant Ce (III)/Ce (IV) coupling sites that react with hydrogen peroxide (H2O2) to produce oxygen, exhibiting catalase (CAT) activity. The multi-cavity structure of Ce-UiO-66 can generate electron holes, and its pore channels can act as micro-reactors to further enhance its ROS scavenging capacity. Additionally, the porous structure of Ce-UiO-66 and the oxygen produced by its reaction with H2O2 may enhance the cavitation effects of ultrasound, thereby improving thrombolysis efficacy. An inflammation-targeting nanodrug, Ce-MOF-CM, prepared by coating reactive oxygen species scavenging Ce-UiO-66 with low-immunogenic mesenchymal stem cell membranes, is applied in combination with external ultrasound stimulation for thrombolytic therapy in rat femoral artery. The porous structure of Ce-UiO-66 and the oxygen produced by its reaction with H2O2 may enhance the cavitation effects of ultrasound, thereby improving thrombolysis efficacy. image