Dual-driven selenium Janus single-atom nanomotors for autonomous regulating mitochondrial oxygen imbalance to catalytic therapy of rheumatoid arthritis

O₂ deficiency and excessive reactive oxygen and nitrogen species (RONS) in macrophage mitochondria is a key factor causing oxygen imbalance in rheumatoid arthritis microenvironment (RAM). Although nanocatalytic therapy that simultaneously produce O₂ and eliminate RONS offer a novel strategy for RA therapy, the therapeutic efficacy of nanozymes is limited by the lack of autonomous targeting into mitochondria. Herein, we constructed a Janus-structured nanomotor (Pd@MSe) with autonomous targeting ability by embedding Pd single-atom nanozymes into mesoporous selenium (MSe) nanozymes, and obtained a composite nanomotor (Pd@MSe-TPP) with dual-driven forces by modifying with triphenylphosphine (TPP) in MSe hemisphere. In RAM, Pd@MSe-TPP nanomotor achieved autonomously target into macrophages mitochondria with the driven of generation O₂ and TPP targeting effect, moreover under the single-atom effect of the Pd nanozymes enhanced electronic transfer between nanozymes, which significantly boosted GPx catalytic activity further effectively enhanced the diffusion of Pd@MSe-TPP nanomotor, thus quickly resorted the oxygen balance. Additionally, while regulating oxygen imbalance, Pd@MSe-TPP nanomotor enable rapidly blocked the inflammatory cascade, restored mitochondrial function and alleviated inflammation, further prevented cartilage degradation and effectively inhibited RA progression. Therefore, the exquisitely designed nanoplatform to regulation arthritic microenvironment provides a new direction for the RA therapy and the clinical translation of nanomedicine.