Thrombus-Targeted Theranostic Microbubbles: A New Technology towards Concurrent Rapid Ultrasound Diagnosis and Bleeding-free Fibrinolytic Treatment of Thrombosis.
Thrombus-Targeted Theranostic Microbubbles: A New Technology towards Concurrent Rapid Ultrasound Diagnosis and Bleeding-free Fibrinolytic Treatment of Thrombosis.
复制标题
DOI：
10.7150/thno.14514
复制
发表时间：
2016
期刊：
影响因子：
12.4
通讯作者：
Peter K
中科院分区：
文献类型：
--
作者：
Wang X;Gkanatsas Y;Palasubramaniam J;Hohmann JD;Chen YC;Lim B;Hagemeyer CE;Peter K
依据：心肌梗死和卒中是发病/死亡的主要原因。典型的基础病理学是血栓/栓子的形成和随后的血管闭塞。全身给予纤溶药物是最有效的药物治疗。然而，出血并发症相对常见，这种风险限制了其更广泛的使用。此外，还没有一种快速的非侵入性成像技术。因此，许多血栓形成事件被遗漏或仅在缺血性损伤已经发生时被诊断。目的：设计和临床前测试一种新的“治疗诊断”技术，用于快速非侵入性诊断和有效的无出血血栓治疗。方法和结果：一种新创建的创新治疗诊断微泡结合了重组纤溶药物，回声增强微泡和重组血栓靶向装置，其形式为活化血小板特异性单链抗体。在初步的体外功能证明后，我们使用氯化铁诱导的颈动脉血栓形成的小鼠模型在超声成像和溶栓治疗中测试了这种治疗诊断微泡。我们证明了可靠的高灵敏度检测体内血栓和监测其尺寸变化的能力，在真实的时间。此外，这些治疗诊断微泡被证明在溶栓方面与商业尿激酶一样有效，但没有尿激酶所见的出血时间延长。结论：我们描述了一种新的治疗诊断技术，能够同时诊断和治疗血栓形成，以及监测溶栓的成功或失败。该技术有望在快速诊断和无出血溶栓方面取得重大进展，从而可能预防许多患者血栓性疾病的破坏性后果。
Rationale: Myocardial infarction and stroke are leading causes of morbidity/mortality. The typical underlying pathology is the formation of thrombi/emboli and subsequent vessel occlusion. Systemically administered fibrinolytic drugs are the most effective pharmacological therapy. However, bleeding complications are relatively common and this risk as such limits their broader use. Furthermore, a rapid non-invasive imaging technology is not available. Thereby, many thrombotic events are missed or only diagnosed when ischemic damage has already occurred. Objective: Design and preclinical testing of a novel 'theranostic' technology for the rapid non-invasive diagnosis and effective, bleeding-free treatment of thrombosis. Methods and Results: A newly created, innovative theranostic microbubble combines a recombinant fibrinolytic drug, an echo-enhancing microbubble and a recombinant thrombus-targeting device in form of an activated-platelet-specific single-chain antibody. After initial in vitro proof of functionality, we tested this theranostic microbubble both in ultrasound imaging and thrombolytic therapy using a mouse model of ferric-chloride-induced thrombosis in the carotid artery. We demonstrate the reliable highly sensitive detection of in vivo thrombi and the ability to monitor their size changes in real time. Furthermore, these theranostic microbubbles proofed to be as effective in thrombolysis as commercial urokinase but without the prolongation of bleeding time as seen with urokinase. Conclusions: We describe a novel theranostic technology enabling simultaneous diagnosis and treatment of thrombosis, as well as monitoring of success or failure of thrombolysis. This technology holds promise for major progress in rapid diagnosis and bleeding-free thrombolysis thereby potentially preventing the often devastating consequences of thrombotic disease in many patients.