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Molecularly Engineered Theranostic Nanoparticles for Thrombosed Vessels: H2O2-Activatable Contrast-Enhanced Photoacoustic Imaging and Antithrombotic Therapy
ACS Nano ( IF 17.1 ) Pub Date : 2018-01-02 00:00:00 , DOI: 10.1021/acsnano.7b06560
Eunkyeong Jung 1 , Changsun Kang 1 , Jeonghun Lee 1 , Donghyuck Yoo 1 , Do Won Hwang 2 , Dohyun Kim 2 , Seong-Cheol Park 3 , Sang Kyoo Lim 4 , Chulgyu Song 5 , Dongwon Lee 1, 6
Affiliation  

A thrombus (blood clot), composed mainly of activated platelets and fibrin, obstructs arteries or veins, leading to various life-threatening diseases. Inspired by the distinctive physicochemical characteristics of thrombi such as abundant fibrin and an elevated level of hydrogen peroxide (H2O2), we developed thrombus-specific theranostic (T-FBM) nanoparticles that could provide H2O2-triggered photoacoustic signal amplification and serve as an antithrombotic nanomedicine. T-FBM nanoparticles were designed to target fibrin-rich thrombi and be activated by H2O2 to generate CO2 bubbles to amplify the photoacoustic signal. In the phantom studies, T-FBM nanoparticles showed significant amplification of ultrasound/photoacoustic signals in a H2O2-triggered manner. T-FBM nanoparticles also exerted H2O2-activatable antioxidant, anti-inflammatory, and antiplatelet activities on endothelial cells. In mouse models of carotid arterial injury, T-FBM nanoparticles significantly enhanced the photoacoustic contrast specifically in thrombosed vessels and significantly suppressed thrombus formation. We anticipate that T-FBM nanoparticles hold great translational potential as nanotheranostics for H2O2-associated cardiovascular diseases.

中文翻译:

分子工程治疗血栓形成纳米颗粒:H 2 O 2可激活的对比增强型光声成像和抗血栓治疗

血栓(血凝块)主要由活化的血小板和纤维蛋白组成,会阻塞动脉或静脉,导致各种威胁生命的疾病。受血栓独特的理化特性(例如丰富的纤维蛋白和过高的过氧化氢(H 2 O 2))的启发,我们开发了血栓特异性治疗血栓症(T-FBM)纳米粒子,可以提供H 2 O 2触发的光声信号放大并用作抗血栓形成的纳米药物。T-FBM纳米颗粒设计用于靶向富含纤维蛋白的血栓,并被H 2 O 2激活以生成CO 2气泡以放大光声信号。在幻像研究中,T-FBM纳米粒子以H 2 O 2触发的方式显示出超声/光声信号的显着放大。T-FBM纳米颗粒还对内皮细胞发挥H 2 O 2激活的抗氧化剂,抗炎和抗血小板活性。在小鼠颈动脉损伤模型中,T-FBM纳米颗粒显着增强了血栓血管中的光声对比度,并显着抑制了血栓形成。我们预计,T-FBM纳米粒子具有巨大的翻译潜力,可作为H 2 O 2相关心血管疾病的纳米治疗剂。
更新日期:2018-01-02
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