Antithrombotic Therapy by Regulating the ROS-Mediated Thrombosis Microenvironment and Specific Nonpharmaceutical Thrombolysis Using Prussian Blue Nanodroplets

作者全名："Zhang, Wenli; Wang, Junrui; Xie, Zhuoyan; Zou, Hongmi; Chen, Qiaoqi; Xu, Lian; Hu, Liu; Fang, Ni; Xu, Jie; Zhou, Jun; Liu, Jia; Ran, Haitao; Wang, Zhigang; Zhang, Yu; Guo, Dajing"

作者地址："[Zhang, Wenli; Wang, Junrui; Xu, Lian; Hu, Liu; Fang, Ni; Xu, Jie; Zhou, Jun; Liu, Jia; Zhang, Yu; Guo, Dajing] Chongqing Med Univ, Clin Med Coll 2, Dept Radiol, Chongqing 400010, Peoples R China; [Xie, Zhuoyan] Chinese Acad Sci, Chongqing Gen Hosp, Dept Ultrasound, Chongqing 401121, Peoples R China; [Zou, Hongmi] Chongqing Med Univ, Clin Med Coll 2, Dept Ophthalmol, Chongqing 400010, Peoples R China; [Chen, Qiaoqi; Ran, Haitao; Wang, Zhigang] Chongqing Med Univ, Clin Med Coll 2, Chongqing Key Lab Ultrasound Mol Imaging, Chongqing 400010, Peoples R China; [Chen, Qiaoqi; Ran, Haitao; Wang, Zhigang] Chongqing Med Univ, Clin Med Coll 2, Dept Ultrasound, Chongqing 400010, Peoples R China"

通信作者："Zhang, Y; Guo, DJ (通讯作者)，Chongqing Med Univ, Clin Med Coll 2, Dept Radiol, Chongqing 400010, Peoples R China."

来源：SMALL

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:000764556600001

JCR分区：Q1

影响因子：13.3

年份：2022

卷号：18

期号：15

开始页：　

结束页：　

文献类型：Article

关键词：thrombosis; Prussian blue; microenvironment regulation; optical droplet vaporization; photothermal therapy

摘要："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 (O-2), 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."

基金机构："National Natural Science Foundation of China [81971608, 81901807, 81701650, 82102063]; Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University [CQYC2020030389, 2020-7]"

基金资助正文："W.Z. and J.W. contributed equally to this work. This study was financially supported by the National Natural Science Foundation of China (Grant Nos. 81971608, 81901807, 81701650, and 82102063) and the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University (No. CQYC2020030389, 2020-7)."