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Exploring novel applications of contemporary therapeutic approaches like chemo\u2010radiotherapy is promising as a highly effective strategy for RA. Herein, a novel activatable nanoradiosensitizer\u201040 (denoted as IRnR\u201040) is developed, based on encapsulating the clinically approved drugs cisplatin (DDP) and indocyanine green (ICG) within a gelatin shell to achieve second near\u2010infrared fluorescence (NIR\u2010II FL) imaging\u2010guided safe\u2010dose synergetic chemo\u2010radiotherapy. The high concentration of matrix metalloproteinase\u20109 (MMP\u20109) in the RA microenvironment plays a pivotal role in triggering the responsive degradation of IRnR\u201040, leading to the rapid release of functional molecules DDP and ICG. The released ICG serves the dual purpose of illuminating the inflamed joints to facilitate accurate target volume delineation for guiding radiotherapy, as well as acting as a real\u2010time reporter for quantifying the release of DDP to monitor efficacy. Meanwhile, the released DDP achieves highly effective synergistic chemotherapy and radiosensitization for RA via the dual reactive oxygen species (ROS)\u2010mediated mitochondrial apoptotic pathway. To sum up, this activatable nanoradiosensitizer IRnR\u201040 is believed to be the first attempt to achieve efficient NIR\u2010II FL imaging\u2010guided safe\u2010dose chemo\u2010radiotherapy for RA, which provides a new paradigm for precise theranostics of refractory benign diseases.<\/jats:p>","DOI":"10.1002\/advs.202308905","type":"journal-article","created":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T01:29:55Z","timestamp":1709170195000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["A Novel Activatable Nanoradiosensitizer for Second Near\u2010Infrared Fluorescence Imaging\u2010Guided Safe\u2010Dose Synergetic Chemo\u2010Radiotherapy of Rheumatoid Arthritis"],"prefix":"10.1002","volume":"11","author":[{"given":"Yarong","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Radiology Fifth Hospital of Shanxi Medical University (Shanxi Provincial People's Hospital)  Taiyuan 030000 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