Microenvironment‐Activatable Probe for Precise NIR‐II Monitoring and Synergistic Immunotherapy in Rheumatoid Arthritis

Abstract Rheumatoid arthritis (RA) represents an insidious autoimmune inflammatory disorder that severely lowers the life quality by progressively destructing joint functions and eventually causing permanent disability, posing a serious public health problem. Here, an advanced theranostic probe is introduced that integrates activatable second near‐infrared (NIR‐II) fluorescence imaging for precise RA diagnosis with multi‐pronged RA treatments. A novel molecular probe comprising a long‐wavelength aggregation‐induced emission unit and a manganese carbonyl cage motif is synthesized, which enables NIR‐II fluorescence activation and concurrently releasing therapeutic carbon monoxide (CO) gas in inflamed joint microenvironment. This molecular probe self‐assembles into a biocompatible nanoprobe, which is subsequently conjugated with anti‐IL‐6R antibody to afford active‐targeting ability of RA. The nanoprobe exhibits significant turn‐on NIR‐II fluorescence signal at the RA lesion, enabling highly sensitive RA diagnosis and real‐time therapeutic monitoring. The combination of ROS scavenging, on‐demand CO gas release, and IL‐6 signaling blockade results in potent therapeutic effect and synergistic immunomodulation impact, significantly alleviating the RA symptoms and preventing joint destruction. This research introduces a novel paradigm for the development of high‐performance, activatable theranostic strategies to facilitate precise detection and enhanced treatment of RA‐related diseases.