Stimulus-responsive AIE nanoassembly for NIR-II imaging-guided cascade photothermal/photodynamic/gas synergistic thrombolysis and vascular healing.

Abstract

Thrombosis remains a major contributor to cardiovascular diseases globally, yet current therapeutic strategies are hindered by narrow therapeutic windows, suboptimal thrombolytic efficacy, and inflammation-driven recurrence. Herein, we reported a second near-infrared (NIR-II) fluorescence imaging (FLI)-guided cascade thrombolytic nanoassembly, MTQPL-Arg@RGD, integrating thrombolytic, antioxidant, and anti-inflammatory functions. This multifunctional nanoassembly was constructed from an aggregation-induced emission (AIE)-active phototheranostic agent (MTQPL), a stimulus-responsive NO donor (l-arginine) and the thrombus-homing peptide c(RGDfC). The integration of NIR-II FLI and AIE sensitively delineated the thrombus site, providing accurate guidance for thrombolysis. Upon 808 nm laser irradiation, the nanoassembly enabled non-invasive and safe thrombolytic therapy through synergistic photothermal/photodynamic (PTT/PDT) effects and hydrogen peroxide-triggered NO gas therapy (GT). Furthermore, it scavenged 82 % of excessive reactive oxygen species, significantly alleviating oxidative stress-induced pro-inflammatory cytokines production. Consequently, 78 % blood reperfusion was realized, effectively restoring blood flow and preventing re-embolism in carotid thrombosis models. This work presents the first multimodal stimulus-responsive nanoassembly for cascade diagnosis and therapy that integrates NIR-II FLI, PTT, PDT, GT, and antioxidant/anti-inflammatory effects, providing a safe, rapid, and minimally invasive approach for time-critical clinical thrombolysis.