Targeted Ruthenium‐Based Anti‐Inflammatory Nanoagent for Enhanced Rheumatoid Arthritis Treatment

The inhibition of joint synovial inflammation, caused by poor oxygen (O₂) supply and excessive reactive oxygen species (ROS) generation, is an important treatment strategy for rheumatoid arthritis (RA). Herein, we formulated a targeted ruthenium-based anti-inflammatory nanosystem consisting of ruthenium clusters-loaded F127-organosilica micelles with folic acid (FA) modification (RuFOMs-FA) for RA treatment through a two-stage macrophage regulatory mechanism. At the first stage, RuFOMs-FA exhibited excellent photothermal capability with a high photothermal conversion efficiency of 55.3% upon external-field 808 nm NIR irradiation, which further induced the death of M1 macrophages through the folic acid-mediated active targeting pathway. Further, the resultant nanoagent mimicked enzymes displayed catalase-like and superoxide dismutase-like activities for endogenously scavenging ROS and producing O₂ to induce the polarization of pro-inflammatory M1 to anti-inflammatory M2 macrophages in the RA physiological environment. More importantly, RuFOMs-FA effectively alleviated hypoxia, inflammation, and cartilage destruction in the synovial joints in a rat RA model by the two-stage macrophage regulatory mechanism. Consequently, it is highly expected that the developed RuFOMs-FA could be applied as a new noble metal-based anti-inflammatory candidate nanosystem for efficient and safe RA treatment.