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Engineered Nanoplatelets for Targeted Delivery of Plasminogen Activators to Reverse Thrombus in Multiple Mouse Thrombosis Models |
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| Authors: | Junchao Xu Yinlong Zhang Jiaqi Xu Guangna Liu Chunzhi Di Xiao Zhao Xiang Li Yao Li Ningbo Pang Chengzhi Yang Yanyi Li Bozhao Li Zefang Lu Meifang Wang Kesheng Dai Rong Yan Suping Li Guangjun Nie |
| Affiliation: | 1. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190 China Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049 China;2. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190 China;3. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190 China College of Pharmaceutical Science, Jilin University, Changchun, 130021 China;4. State Key Laboratory of Natural Medicines, China Pharmaceutical University, School of Basic Medical Sciences and Clinical Pharmacy, Nanjing, 210009 China;5. Jiangsu Institute of Hematology, The First Affiliated Hospital, Collaborative Innovation Center of Hematology, Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, 215006 China;6. Department of Cardiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050 China |
| Abstract: | Rapid cut-off of blood supply in diseases involving thrombosis is a major cause of morbidity and mortality worldwide. However, the current thrombolysis strategies offer limited results due to the therapeutics' short half-lives, low targeting ability, and unexpected bleeding complications. Inspired by the innate roles of platelets in hemostasis and pathological thrombus, platelet membrane-camouflaged polymeric nanoparticles (nanoplatelets) are developed for targeting delivery of the thrombolytic drug, recombinant tissue plasminogen activator (rt-PA), to local thrombus sites. The tailor-designed nanoplatelets efficiently accumulate at the thrombi in pulmonary embolism and mesenteric arterial thrombosis model mice, eliciting a significantly enhanced thrombolysis activity compared to free rt-PA. In addition, the nanoplatelets exhibit improved therapeutic efficacy over free rt-PA in an ischemic stroke model. Analysis of in vivo coagulation indicators suggests the nanoplatelets might possess a low risk of bleeding complications. The hybrid biomimetic nanoplatelets described offer a promising solution to improve the efficacy and reduce the bleeding risk of thrombolytic therapy in a broad spectrum of thrombosis diseases. |
| Keywords: | nanoplatelets plasminogen activators targeted drug delivery thrombus |