Peroxisome-inspired self-adaptive multi-fuel-propelled nanomotors for enhanced hyperuricemia improvement and...

Artificial-organelle nanoplatforms, despite holding significant promise, commonly face limited autonomous mobility, microenvironment-responsive localization, and durable circulation. Herein, we report a peroxisome-inspired, self-adaptive, multi-fuel-propelled Janus nanomotor (SMAP) that integrates the multienzyme regulation of uric acid (UA) and reactive oxygen species (ROS) with autonomous propulsion via a spatially separated nanozyme architecture. SMAP consists of hollow C-Fe-N nanospheres asymmetrically decorated with Pt nanoparticles and exhibits robust superoxide dismutase-, catalase-, uricase-, peroxidase-, and oxidase-like activities. It leverages dual endogenous fuel systems (UA + H₂O₂ and O₂•^- + H₂O₂) to enhance autonomous mobility and substrate-guided accumulation in fuel-rich microenvironments. In vitro, SMAP catalyzed UA → allantoin conversion, eliminated harmful H₂O₂ intermediates, and reprogrammed macrophages toward anti-inflammatory phenotypes. In vivo (hyperuricemic mice), SMAP exhibited prolonged circulation, robust UA-lowering efficacy, alleviation of inflammation-associated organ damage, and confirmed biocompatibility. These therapeutic benefits arise primarily from SMAP's multienzyme UA/ROS catalysis. The dual-fuel propulsion increases substrate interaction, barrier crossing, and persistence in UA/ROS-rich microenvironments. Together, these results demonstrate that SMAP is a versatile, peroxisome-inspired nanomotor platform that couples dynamic propulsion with multienzyme UA/ROS regulation, providing an essential strategy for precise management of hyperuricemia and inflammation.