Wang Zhaojian, Pan Yunfan, Huang Huaigu, Zhang Yuan, Li Yan, Zou Chenghong, Huang Guanghua, Chen Yuexin, Li Yongjian, Li Jiang, Chen Haosheng
Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
State Key Laboratory of Tribology, Tsinghua University, Beijing, China.
Front Bioeng Biotechnol. 2022 Jul 22;10:965769. doi: 10.3389/fbioe.2022.965769. eCollection 2022.
There is a need to improve the efficacy and safety of endovascular techniques in venous thrombotic diseases, and microbubble enhanced sonothrombolysis is a promising approach. However, whether endovascular low-frequency ultrasound (LFUS) can be utilized in microbubble enhanced sonothrombolysis is unclear. Here, we present a catheter-based thrombolytic system that combines unfocused low-frequency low-intensity ultrasound with novel fibrin-targeted drug-loaded bifunctional microbubbles. We develop an flow model and an rabbit inferior vena cava (IVC) thrombosis model to evaluate the safety and efficacy of the thrombolytic system. The results indicate that microbubble enhanced sonothrombolysis with endovascular LFUS treatment for 30 min is equally effective compared to pure pharmacologic treatment. Furthermore, the thrombolytic efficacy of this system is safely and substantially improved by the introduction of a fibrin-targeted drug-loaded bifunctional microbubble with a reduction of the fibrinolytic agent dosage by 60%. The microbubble enhanced endovascular LFUS sonothrombolysis system with excellent thrombolytic efficacy may serve as a new therapeutic approach for venous thrombotic diseases.
有必要提高血管内技术在静脉血栓性疾病中的疗效和安全性，微泡增强超声溶栓是一种很有前景的方法。然而，血管内低频超声（LFUS）是否可用于微泡增强超声溶栓尚不清楚。在此，我们展示了一种基于导管的溶栓系统，该系统将非聚焦低频低强度超声与新型纤维蛋白靶向载药双功能微泡相结合。我们建立了一个血流模型和一个兔下腔静脉（IVC）血栓形成模型，以评估该溶栓系统的安全性和有效性。结果表明，与单纯药物治疗相比，血管内LFUS治疗30分钟的微泡增强超声溶栓效果相同。此外，通过引入纤维蛋白靶向载药双功能微泡，该系统的溶栓效果得到了安全且显著的提高，同时纤溶剂剂量减少了60%。具有优异溶栓效果的微泡增强血管内LFUS超声溶栓系统可能成为静脉血栓性疾病的一种新的治疗方法。
