血栓形成和溶解引起的炎症损伤除了血栓本身引起的细胞死亡和器官功能障碍外,还会增加血栓并发症的风险。因此,迫切需要快速精确的溶栓治疗策略,以有效溶解血栓并同时抵抗氧化。在这项研究中,Ce-UiO-66,一种具有活性氧(ROS)清除性能的铈基金属有机骨架(Ce-MOF),由具有炎症靶向特性的低免疫原性间充质干细胞膜封装,用于构建靶向纳米药物Ce-UiO-CM。Ce-UiO-CM联合体外超声刺激用于大鼠股动脉溶栓治疗。Ce-UiO-66具有丰富的Ce(III)/Ce(IV)偶联位点,与过氧化氢(H2O2)反应产生氧气,表现出过氧化氢酶(CAT)活性。Ce-UiO-66的多腔结构可以产生电子空穴,其孔通道可以作为微反应器,进一步提高其清除ROS的能力。此外,Ce-UiO-66的多孔结构及其与H2O2反应产生的氧气可以增强超声的空化效应,从而提高溶栓疗效。
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.