Therapeutic Effect of a Near‐Infrared Responsive MTX‐Mn3O4@PDA Nano‐Delivery System on Rheumatoid Arthritis

Abstract Rheumatoid arthritis (RA) is an autoimmune disease associated with chronic inflammatory processes. RA, which is typically associated with the accumulation of hyperactive immune cells (HICs), particularly M1 proinflammatory macrophages, is accompanied by elevated levels of reactive oxygen species (ROS) and decreased pH in the synovial membranes of the joints. In this work, a nano‐delivery system (MTX‐Mn 3 O 4 @PDA) is designed that can deliver photothermal materials, ROS scavengers, and synovial fibroblast inhibitors at the joint site for the treatment of RA. After injecting MTX‐Mn 3 O 4 @PDA into the inflamed site of RA, photothermal therapy is initiated by near‐infrared (NIR) laser irradiation, which resulted in the death of activated inflammatory cells at the lesion site. While polydopamine (PDA) slowly dissociates under stimulation by a low pH microenvironment. Subsequently, excess ROS interacts with the Mn 3 O 4 nanozyme and the undissociated PDA nanozyme, promoting ROS clearance, while Methotrexate (MTX) inhibits the proliferation of synovial fibroblasts. Intra‐articular injection of MTX‐Mn 3 O 4 @PDA (7 mg kg −1 ) into collagen‐induced arthritis mice demonstrated efficacy in reducing toe swelling and significantly alleviating synovial inflammation, bone erosion, and cartilage degeneration. This nano‐delivery system has potential clinical applications for treating RA.