Engineered platelets-based drug delivery platform for targeted thrombolysis  

作　　者：Songli Wang Ruifeng Wang Nana Meng Linwei Lu Jun Wang Jianfen Zhou Jiasheng Lu Qianzhu Xu Cao Xie Changyou Zhan Yao Li Yang Yu Weiyue Lu Min Liu 

机构地区：[1]Department of Pharmaceutics,School of Pharmacy,Key Laboratory of Smart Drug Delivery(Ministry of Education and PLA),Fudan University,Shanghai 201203,China [2]The Department of Integrative Medicine,Huashan Hospital,Fudan University and the Institutes of Integrative Medicine of Fudan University,Shanghai 200041,China [3]Department of Pharmacology,School of Basic Medical Sciences,Fudan University,Shanghai 200032,China [4]The National Facility for Protein Science in Shanghai(NFPS),Shanghai 201210,China [5]State Key Laboratory of Medical Neurobiology and the Collaborative Innovation Center for Brain Science and Department of Pharmacology,School of Basic Medical Sciences,Fudan University,Shanghai 200032,China [6]Minhang Branch,Zhongshan Hospital and Institute of Fudan-Minhang Academic Health System,Minhang Hospital,Fudan University,Shanghai 201199,China

出　　处：《Acta Pharmaceutica Sinica B》2022年第4期2000-2013,共14页药学学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(No.81690263).

摘　　要：Thrombolytic agents have thus far yielded limited therapeutic benefits in the treatment of thrombotic disease due to their short half-life,low targeting ability,and association with serious adverse reactions,such as bleeding complications.Inspired by the natural roles of platelets during thrombus formation,we fabricated a platelet-based delivery system(NO@uPA/PLTs)comprising urokinase(uPA)and arginine(Arg)for targeted thrombolysis and inhibition of re-embolism.The anchoring of uPA to the platelet surface by lipid insertion increased the thrombotic targeting and in vivo circulation duration of uPA without disturbing platelet functions.Nitric oxide(NO)generated by the loaded Arg inhibited platelet aggregation and activation at the damaged blood vessel,thereby inhibiting re-embolism.NO@uPA/PLTs effectively accumulated at the thrombi in pulmonary embolism and carotid artery thrombosis model mice and exerted superior thrombolytic efficacy.In addition,the platelet delivery system showed excellent thrombus recurrence prevention ability in a mouse model of secondary carotid artery injury.The coagulation indicators in vivo showed that the platelet-based uPA and NO co-delivery system possessed a low hemorrhagic risk,providing a promising tool for rapid thrombolysis and efficient inhibition of posttreatment re-embolism.

关 键 词：PLATELET UROKINASE Nitric oxide Targeted thrombolysis Thrombus reformation 

分 类 号：R943[医药卫生—药剂学]