Platelet Membrane-Coated r-SAK Improves Thrombolytic Efficacy by Targeting Thrombus.

Autor: Hua R; Department of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China., Li M; State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, China., Lin Q; Department of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China., Dong M; Department of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China., Gong X; Department of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China., Lin Z; Department of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China., Li Y; College of Letters and Science, University of Wisconsin-Madison, Madison, Wisconsin 53715-1007, United States., Li C; Department of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China., Wu T; Department of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China., Tan C; Department of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China., Zhang W; Department of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China., Wang Q; Department of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China., Wu T; Department of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China., Zhou X; Department of Blood Transfusion, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China., Yang F; State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, China., Li C; Department of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
Jazyk: angličtina
Zdroj: ACS applied materials & interfaces [ACS Appl Mater Interfaces] 2024 May 01; Vol. 16 (17), pp. 21438-21449. Date of Electronic Publication: 2024 Apr 16.
DOI: 10.1021/acsami.3c18402
Abstrakt: Thrombolytic therapy is one of the most effective treatments for thrombus dissolution and recanalization of blocked vessels in thrombotic diseases. However, the application of the thrombolytic strategy has been limited due to unsatisfactory thrombolytic efficacy, relatively higher bleeding complications, and consequently restricted indications. Recombinant staphylokinase (r-SAK) is a third-generation thrombolytic agent produced by genetic engineering technology, which exhibits a better thrombolytic efficacy than urokinase and recombinant streptokinase. Inspired by the natural affinity of platelets in hemostasis and pathological thrombosis, we developed a platelet membrane (PM)-coated r-SAK (PM-r-SAK). Results from animal experiments and human in vitro studies showed that the PM-r-SAK had a thrombolytic efficacy equal to or better than its 4-fold dose of r-SAK. In a totally occluded rabbit femoral artery thrombosis model, the PM-r-SAK significantly shortened the initial recanalization time compared to the same dose and 4-fold dose of r-SAK. Regarding the recanalized vessels, the PM-r-SAK prolonged the time of reperfusion compared to the same dose and 4-fold dose of r-SAK, though the differences were not significant. An in vitro thrombolytic experiment demonstrated that the thrombolytic efficacy of PM-r-SAK could be inhibited by platelet-poor plasma from patients taking aspirin and ticagrelor. PM coating significantly improves the thrombolytic efficacy of r-SAK, which is related to the thrombus-targeting activity of the PM-r-SAK and can be inhibited by aspirin- and ticagrelor-treated plasma.
Databáze: MEDLINE
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