Near-Infrared Laser-Activatable Core–Shell Platforms with Photothermal–Enzymatic Capacity against Lower Limb Thrombosis

Acute lower limb ischemia poses serious clinical challenges, necessitating innovative therapeutic strategies beyond conventional catheter-directed thrombolysis. Herein, a multifunctional platform has been developed by combining photothermal thrombolysis and enzymatic thrombolysis for treating lower limb thrombosis. The platform comprises gold nanorods enveloped by mesoporous silica nanoshells (Au@MSN), loaded with urokinase and functionalized with PEGylated lipids. The positively charged platform exhibits a high surface area of 510.0 m²/g and mesopores, enabling urokinase loading efficacy of 32.6% and activatable release of urokinase under different conditions. Under 915 nm laser irradiation, the platform with good biocompatibility exhibits dual functionality as the localized hyperthermia generation for thrombus disruption and responsive urokinase release. <i>In vitro</i> evaluation revealed a remarkable thrombolysis rate of 71.6%. <i>In vivo</i> studies confirmed the effective restoration of vascular patency in lower limb thrombosis models through the platform combined with light irradiation. This work offers suggestions for developing activatable modalities in thrombolytic treatments.