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

ABSTRACT The inhibition of joint synovial inflammation, caused by poor oxygen (O 2 ) 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 O 2 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.