A magnetic hyperthermia-chemodynamic nanoreactor with ascorbic acid-enhanced reactive oxygen species regulation for anti-thrombosis therapy

Abstract

The synergy of reactive oxygen species (ROS) and heat has shown promise in enhancing thrombolysis by disrupting fibrin structure. However, precise control over the spatiotemporal distribution and dosage of ROS and heat at deep thrombus sites remains challenging. Here, we report an ascorbic acid (AA)-enhanced magnetic hyperthermia-chemodynamic therapy (MH-CDT) that exploits the concentration-dependent dual functionality of AA for precision thrombolysis. A dual-targeted magnetic nanoreactor (CMPV) was engineered to rapidly accumulate at the thrombus site via magnetic guidance and platelet membrane coating. AA facilitates the Fenton reaction for enhanced ROS generation to dissolve fibrin, while subsequently neutralizing excessive ROS to suppress inflammation during vascular repair. MH-CDT demonstrated thorough thrombus clearance and vascular recovery within 24 h without thrombosis recurrence in a mouse carotid artery thrombosis model. The combination between magnetic hyperthermia-induced fibrin disruption and AA-mediated ROS modulation enabled efficient thrombolysis while minimizing detrimental effects on the vascular endothelium. This AA-enhanced MH-CDT system provides a precise and effective thrombolytic strategy that overcomes depth limitations, showing promise for clinical translation.