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Here, an advanced theranostic probe is introduced that integrates activatable second near\u2010infrared (NIR\u2010II) fluorescence imaging for precise RA diagnosis with multi\u2010pronged RA treatments. A novel molecular probe comprising a long\u2010wavelength aggregation\u2010induced emission unit and a manganese carbonyl cage motif is synthesized, which enables NIR\u2010II fluorescence activation and concurrently releasing therapeutic carbon monoxide (CO) gas in inflamed joint microenvironment. This molecular probe self\u2010assembles into a biocompatible nanoprobe, which is subsequently conjugated with anti\u2010IL\u20106R antibody to afford active\u2010targeting ability of RA. The nanoprobe exhibits significant turn\u2010on NIR\u2010II fluorescence signal at the RA lesion, enabling highly sensitive RA diagnosis and real\u2010time therapeutic monitoring. The combination of ROS scavenging, on\u2010demand CO gas release, and IL\u20106 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\u2010performance, activatable theranostic strategies to facilitate precise detection and enhanced treatment of RA\u2010related diseases.<\/jats:p>","DOI":"10.1002\/adma.202409661","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T00:12:25Z","timestamp":1728259945000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Microenvironment\u2010Activatable Probe for Precise NIR\u2010II Monitoring and Synergistic Immunotherapy in Rheumatoid Arthritis"],"prefix":"10.1002","volume":"36","author":[{"given":"Yuan","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology Frontiers Science Center for Cell Responses Key Laboratory of Bioactive Materials Ministry of Education, and College of Life Sciences Nankai University  Tianjin 300071 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