Antithrombotic Therapy by Regulating the ROS-Mediated Thrombosis Microenvironment and Specific Nonpharmaceutical Thrombolysis Using Prussian Blue Nanodroplets.
Antithrombotic Therapy by Regulating the ROS-Mediated Thrombosis Microenvironment and Specific Nonpharmaceutical Thrombolysis Using Prussian Blue Nanodroplets.
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通过调节 ROS 介导的血栓形成微环境和使用普鲁士蓝纳米液滴进行特异性非药物溶栓进行抗血栓治疗。
DOI：
10.1002/smll.202106252
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发表时间：
2022-03
期刊：
影响因子：
13.3
通讯作者：
Dajing Guo
中科院分区：
文献类型：
--
作者：
Wenli Zhang;Junrui Wang;Zhuoyan Xie;Hongmi Zou;Qiaoqi Chen;Lian Xu;Liu Hu;Ni Fang;Jie Xu;Jun Zhou;Jia Liu;Haitao Ran;Zhigang Wang;Yu Zhang;Dajing Guo
在血栓性疾病中，活性氧（ROS）介导的氧化应激作为血栓形成的“肇事者”的影响必须得到解决。因此，对血栓治疗的理解不足促使作者寻求更全面和有效的抗血栓治疗策略。设计了基于普鲁士蓝（PB）的纳米液滴系统（PB-PFP@PC），其在核心中使用PB和全氟戊烷（PFP），并且靶向肽（CREKA，Cys-Arg-Glu-Lys-Ala）连接到作为递送载体壳的聚（乳酸-共乙醇酸）（PLGA）。在近红外（NIR）激光照射下，PB和PFP共同实现了前所未有的无药物溶栓双重策略：光热治疗（PTT）结合光学液滴汽化（ODV）。PB是一种纳米酶，也通过其抗氧化活性调节血管微环境，以持续抑制异常升高的ROS，并相应地减少血栓部位的炎症因子。这项研究不仅证明了ODV在血栓治疗中的潜力，而且还证明了由于热消融诱导的纤维蛋白网络结构损伤导致的PTT溶栓的机制。此外，PB催化ROS产生氧气（O2），与ODV效应结合，增强超声信号。因此，通过PB纳米滴调节血栓形成微环境结合特异性非药物溶栓提供了更全面和有效的抗血栓形成治疗策略。
In thrombotic diseases, the effects of reactive oxygen species (ROS)-mediated oxidative stress as a "perpetrator" in thrombosis must be resolved. Accordingly, an insufficient understanding of thrombus therapy prompted the authors to pursue a more comprehensive and efficient antithrombotic treatment strategy. A Prussian blue (PB)-based nanodroplet system (PB-PFP@PC) is designed using PB and perfluorinated pentane (PFP) in the core, and a targeting peptide (CREKA, Cys-Arg-Glu-Lys-Ala) is attached to poly(lactic-coglycolic acid) (PLGA) as the delivery carrier shell. Upon near-infrared (NIR) laser irradiation, PB and PFP jointly achieve an unprecedented dual strategy for drug-free thrombolysis: photothermal therapy (PTT) combined with optical droplet vaporization (ODV). PB, a nanoenzyme, also regulates the vascular microenvironment via its antioxidant activity to continuously scavenge abnormally elevated ROS and correspondingly reduce inflammatory factors in the thrombus site. This study provides a demonstration of not only the potential of ODV in thrombus therapy but also the mechanism underlying PTT thrombolysis due to thermal ablation-induced fibrin network structural damage. Moreover, PB catalyzes ROS to generate oxygen (O2 ), which combines with the ODV effect, enhancing the ultrasound signal. Thus, regulation of the thrombosis microenvironment combined with specific nonpharmaceutical thrombolysis by PB nanodroplets provides a more comprehensive and efficient antithrombotic therapeutic strategy.
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