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Therefore, developing effective radiosensitizers with monitoring of tumor response is of great significance for precise radiotherapy. Herein, a novel radiosensitizer (term as: SCuFs) is developed, consisting of traditional Chinese medicine (TCM) compounds salidroside, Cu<jats:sup>2+<\/jats:sup>, and hydroxyl radical (\u2022OH) activated second near\u2010infrared window fluorescence (NIR\u2010II FL) molecules, which make the radiosensitization effect and boosted chemodynamic therapy (CDT) efficacy. The overexpressed glutathione in the tumor induces the SCuFs dissociation, allowing deep penetration of the drug to the whole tumor region. After X\u2010ray irradiation, salidroside inhibits the Nuclear factor erythroid 2\u2010like 2 (Nrf2)protein expression and blocks cells in the G2\/M phase with the highest radiosensitivity, which amplifies the reactive oxygen species (ROS) generation to exacerbate DNA damage, thus achieving radiosensitization. Meanwhile, the upregulated ROS provides sufficient chemical fuel for Cu<jats:sup>+<\/jats:sup>\u2010mediated CDT to produce more \u2022OH. NIR\u2010II FL imaging can monitor the \u2022OH changes during the therapy process, confirming the radiosensitization effect and CDT process related to \u2022OH. This study not only achieves effective radiosensitization and cascaded ROS\u2010mediated CDT efficacy, but also provides a useful tool for monitoring therapeutic efficacy, showing great prospects for clinical application.<\/jats:p>","DOI":"10.1002\/adma.202413226","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T07:28:21Z","timestamp":1744097301000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["A Salidroside\u2010Based Radiosensitizer Regulates the Nrf2\/ROS Pathway for X\u2010Ray Activated Synergistic Cancer Precise Therapy"],"prefix":"10.1002","volume":"37","author":[{"given":"Qingqing","family":"Li","sequence":"first","affiliation":[{"name":"Fujian Science &amp; Technology Innovation Laboratory for Optoelectronic Information of China College of Chemistry Fuzhou University  Fuzhou 350108 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