Magnetic/photothermal dual-driven micro/nanorobots for synergistic NO-mediated photothermal thrombolysis

Thrombotic vascular obstruction, a leading cause of cardiovascular/cerebrovascular events and global mortality, poses a severe threat to human health, while conventional thrombolytic agents suffer from inherent limitations, including short half-lives, poor targeting, low utilization efficiency, and suboptimal therapeutic outcomes. Nitric oxide (NO)-supported gas therapy exhibits significant potential in synergistic thrombolysis but is hindered by its ultra-short half-life and challenges in targeted delivery and spatiotemporal control. Herein, we developed dual-driven rGO@Fe₃O₄-βCD-BNN6 micro/nanorobots for NO-mediated targeted photothermal thrombus ablation, with the advantages of site-specific accumulation, controlled therapeutic agent release, and enhanced therapeutic specificity. Reduced graphene oxide (rGO) served as the core photothermal agent with excellent photothermal conversion efficiency (44.2%), while Fe₃O₄ nanoparticles endowed the micro/nanorobots with magnetic responsiveness for precise directional targeting. β-Cyclodextrin (βCD) enhanced the loading capacity and biocompatibility of the NO donor BNN6 (N,N'-di-sec-butyl-N,N'-dinitroso-1,4-phenylene diamine), which underwent photothermal-induced thermal decomposition to release NO in situ, disrupting fibrin networks and synergistically boosting thrombolysis. The micro/nanorobots achieved a remarkable thrombolytic efficacy of up to 88.8%, significantly outperforming conventional drugs. Comprehensive hemolysis and cytotoxicity assays confirmed their excellent biocompatibility. This dual-driven, photothermal-gas synergistic micro/nanorobotic platform provides a novel and safe strategy to overcome the limitations of traditional thrombolysis, paving the way for advancing micro/nanorobotic thrombotic intervention.