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.
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