Platelet membrane-functionalized hollow mesoporous Prussian blue nanomedicine for comprehensive thrombolytic management by targeted enhanced fibrinolysis and ROS scavenging

Thrombotic diseases cause significant risks of disability and death worldwide. However, conventional thrombolytic drugs have short half-lives, poor targeting capabilities, limited therapeutic effects，   and narrow therapeutic windows. Moreover, most basic studies   focus only on thrombolytic efficiency and ignore the inflammatory factors that promote thrombosis progression, such as reactive oxygen species   (ROS)-mediated oxidative stress. Therefore, to achieve comprehensive and effective thrombolytic management, both targeted thrombolytic therapy and the elimination of inflammatory factors must be achieved. In this study, we developed a platelet membrane (PM)-functionalized hollow mesoporous Prussian blue nanomedicine (HMPB-rtPA@PM), which was innovatively coassembled from two FDA-approved drugs (Prussian blue (PB) and alteplase (rtPA)) and showed marked advantages in both thrombi targeting and photothermal/pharmacological synergistic fibrinolysis. Moreover, HMPB-rtPA@PM exhibited the potential to inhibit platelet aggregation and regulate the inflammatory microenvironment by scavenging ROS. As expected, this nanomedicine not only achieved more efficient thrombolysis in both thrombus models but also delayed thrombosis progression through therapeutic visualization in the black tail model. Such rational therapeutic principle provides a broad platform for the comprehensive management of thrombotic diseases.