A Synergistic and Efficient Thrombolytic Nanoplatform: A Mechanical Method of Blasting Combined with Thrombolytic Drugs

作者全名："Hu, Liu; Xu, Jie; Zhang, Wenli; Wang, Junrui; Fang, Ni; Luo, Ying; Xu, Lian; Liu, Jia; Zhang, Yu; Ran, Haitao; Guo, Dajing; Zhou, Jun"

作者地址："[Hu, Liu; Xu, Jie; Zhang, Wenli; Wang, Junrui; Fang, Ni; Luo, Ying; Xu, Lian; Liu, Jia; Zhang, Yu; Guo, Dajing; Zhou, Jun] Chongqing Med Univ, Affiliated Hosp 2, Dept Radiol, Chongqing, Peoples R China; [Hu, Liu; Zhang, Wenli; Wang, Junrui; Fang, Ni; Luo, Ying; Xu, Lian] Chongqing Med Univ, Chongqing Key Lab Ultrasound Mol Imaging & Dept Ul, Affiliated Hosp 2, Chongqing, Peoples R China; [Hu, Liu; Zhang, Wenli; Wang, Junrui; Fang, Ni; Luo, Ying; Xu, Lian] Chongqing Med Univ, Affiliated Hosp 2, Dept Ultrasound, Chongqing, Peoples R China; [Ran, Haitao] Chongqing Med Univ, Affiliated Hosp 2, Inst Ultrasound Imaging, Dept Ultrasound, Chongqing, Peoples R China"

通信作者："Zhou, J (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Radiol, Chongqing, Peoples R China."

来源：INTERNATIONAL JOURNAL OF NANOMEDICINE

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000884452200001

JCR分区：Q1

影响因子：8

年份：2022

卷号：17

期号：　

开始页：5229

结束页：5246

文献类型：Article

关键词：low-intensity focused ultrasound; thrombolysis; PFH; rtPA; phase transition

摘要："Background and Objective: Thrombosis is a common disease that poses a great threat to life and health. Most thrombolytic effects of traditional treatments or nanomedicine are not efficient or safe enough. Therefore, we designed a nanoparticle (NP) with a combination of a phase transition material and thrombolytic drugs for efficient and safe thrombolysis.Methods: A thrombus fibrin-targeted and phase transition NP was designed and contained perfluorohexane (PFH) and the thrombo-lytic drug rtPA core, with CREKA polypeptides attached to the shell of the PLGA NPs. Characterization of the phase transition and ultrasound imaging of the NPs was carried out under low-intensity focused ultrasound (LIFU). LIFU-responsive drug release in vitro was also explored. Under the synergistic effect of PFH and rtPA, the efficient thrombolysis ability of the NPs was studied in vitro and in vivo. In vivo monitoring of thrombosis and biosafety were also verified.Results: The PPrC NPs had good ultrasound imaging ability under LIFU irradiation and were related to the phase transition characteristics of the NPs. CREKA polypeptides can effectively increase the aggregation of the NPs on thrombi. Under static and dynamic conditions in vitro, the ""liquid to gas"" transformation effect of PFH can perform the destruction function of the excavator at the thrombus site and promote the specific release of rtPA, and the subsequent rtPA drug thrombolysis can further fully dissolve the thrombus. In vivo experiments showed that the NPs can monitor the formation of thrombi and have good thrombolytic effects, with significantly reduced bleeding side effects. The biochemical indexes of the rats were within normal limits after treatment.Conclusion: PPrC NPs loaded with PFH and rtPA combining a mechanical way of blasting with thrombolytic drugs may be a promising new and reliable approach for thrombus monitoring and treatment."

基金机构：National Natural Science Foundation of China; Chongqing Natural Science Foundation; Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University; [81971608]; [81901807]; [81701650]; [82102063]; [cstc2021jcyj-msxmX0210]; [2020-7]; [2021-24]

基金资助正文："Acknowledgments This work was financially supported by the National Natural Science Foundation of China (grant Nos. 81971608, 81901807, 81701650, 82102063) , the Chongqing Natural Science Foundation (cstc2021jcyj-msxmX0210) and the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University (2020-7, 2021-24) . Liu Hu and Jie Xu are co -first authors for this study."