NIR-Propelled Thermosensitive Bowl-Shaped Nanomotors with High Penetration and Targeting for Photoacoustic Imaging Guided Thrombolysis Therapy.

Abstract

Traditional antithrombotic therapeutic strategies encounter challenges including heightened bleeding risks, short circulation times, low targeting ability, and inferior thrombus penetration. Therefore, a novel thrombolysis nanodrug (APBUL) is designed that incorporates urokinase (UK) loaded onto the surface of bowl-shaped nanomotors (APBs) encapsulated within fibrin peptide (CREKA)-modified thermosensitive liposomes, presenting an innovative therapeutic platform for thrombolysis. APBUL leverages CREKA's targeting ability for thrombus accumulation. Subsequently, under the irradiation of near-infrared light, the thermosensitive liposomal shell undergoes controlled disruption, releasing internal APBs and UK. Then, the APBs move directionally though thermophoresis effect, facilitating photothermal therapy and deep thrombus penetration, and synergistically enhancing UK release and diffusion to optimize thrombolysis. Moreover, the APBUL possesses a catalase-like activity, catalyzing hydrogen peroxide into oxygen to alleviate oxidative stress and inflammatory factors at the thrombus site, thereby lowering the recurrence risk. Combined with the ability of APBUL's photoacoustic imaging, this new strategy is expected to provide an inspiring idea for the integrated use of clinical thrombolytic therapy in diagnosis, imaging, and treatment.