Metal–Organic-Framework-Derived Carbon Nanostructures for Site-Specific Dual-Modality Photothermal/Photodynamic Thrombus Therapy

Abstract

Although near-infrared (NIR)-light-mediated photothermal thrombolysis has been investigated to overcome the bleeding risk of clinical clot-busting agents, the secondary embolism of post-phototherapy fragments (>10 µm) for small vessels should not be ignored in this process. In this study, dual-modality photothermal/photodynamic thrombolysis is explored using targeting nanoagents with an emphasis on improving biosafety as well as ameliorating the thrombolytic effect. The nanoagents can actively target glycoprotein IIb/IIIa receptors on thrombus to initiate site-specific thrombolysis by hyperthermia and reactive oxygen species under NIR laser irradiation. In comparison to single photothermal thrombolysis, an 87.9% higher re-establishment rate of dual-modality photothermal/photodynamic thrombolysis by one-time treatment is achieved in a lower limb thrombosis model. The dual-modality thrombolysis can also avoid re-embolization after breaking fibrin into tiny fragments. All the results show that this strategy is a safe and validated protocol for thrombolysis, which fits the clinical translational trend of nanomedicine.