By further rebalancing the Keap1-Nrf2 axis and suppressing MAPK/NF-κB signaling, the nano-immunomodulator achieves synergistic microenvironment remodeling, integrating pyroptosis inhibition, immunomodulation, and osteogenic repair, offering a promising nanotherapeutic strategy for RA treatment. Here, KEAP1 is linked to rheumatoid arthritis.