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

Abstract

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.

Keywords

Thrombus targeting / Thermosensitive liposome / Controlled drug release / Penetration / Integrated attack and defense thrombolytic

Conflicts of interest

The authors declare no conflicts of interest in this work.

Acknowledgments

This work was supported by National Natural Science Foundation of China (No.82102918).

Supplementary materials

Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.ajps.2025.101035.

The figures and tables with "S" before the serial number are included in the Supplementary material.

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