Department of Cardiovascular Surgery, Reiji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
Adv Sci (Weinh). 2024 May;11(20):e2304441. doi: 10.1002/advs.202304441. Epub 2024 Apr 4.
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 (HO) 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 HO may enhance the cavitation effects of ultrasound, thereby improving thrombolysis efficacy.
血栓形成和溶解引起的炎症损伤会增加血栓本身引起的细胞死亡和器官功能障碍之外的血栓性并发症的风险。因此,急需一种快速、精确的溶栓治疗策略,以有效地同时溶解血栓和抵抗氧化。在这项研究中,Ce-UiO-66 是一种具有活性氧(ROS)清除特性的基于铈的金属有机骨架(Ce-MOF),由具有炎症靶向特性的低免疫原性间充质干细胞膜包裹,用于构建靶向纳米药物 Ce-UiO-CM。Ce-UiO-CM 与外部超声刺激联合应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,可与过氧化氢(HO)反应生成氧气,表现出过氧化氢酶(CAT)活性。Ce-UiO-66 的多腔结构可产生电子空穴,其孔道可作为微反应器,进一步增强其 ROS 清除能力。此外,Ce-UiO-66 的多孔结构以及其与 HO 反应产生的氧气可能会增强超声空化效应,从而提高溶栓效果。