Dual-responsive and NIR-triggered detachable nanoplatform for integrated thrombolytic and antiplatelet therapy.

To develop an efficient thrombolytic therapy approach that addresses the limitations of current fibrinolytic drugs, such as short half-life, weak thrombus specificity and poor penetration ability, we constructed a NIR-triggered detachable nanoplatform (PA/UK@IcpLipo) using thin-film hydration method. It was designed to integrate attack and defense mechanisms for thrombolytic therapy. This platform can actively identify thrombi by binding to GPIIb-IIIa receptors overexpressed on activated platelets. Upon NIR laser activation and interaction with thrombin in the thrombotic microenvironment, the thermosensitive liposomes rupture, releasing the PA/UK core for deep penetration into the thrombus. Our results showed that the PA/UK@IcpLipo nanoplatform efficiently promoted rapid thrombolysis under the action of UK (attack), followed by PA exerting an antiplatelet aggregation effect (defense). This dual-action approach significantly improved vascular reperfusion rates. The NIR-triggered detachable nanoplatform offered a promising solution for enhanced thrombolysis efficiency and reduced bleeding risk, addressing critical limitations of current fibrinolytic therapies.