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Precise and real\u2010time visualization of NTR activity is therefore critical for understanding disease mechanisms and enabling accurate diagnosis and targeted therapy. Fluorescent probes have emerged as powerful and versatile chemical biology tools for NTR sensing owing to their high sensitivity, selectivity, and spatiotemporal resolution. Recent advances in two\u2010photon fluorescence imaging, second near\u2010infrared (NIR\u2010II) fluorescence imaging, and time\u2010resolved fluorescence imaging have markedly enhanced tissue penetration and quantitative accuracy, thereby enabling reliable detection of NTR activity in complex biological environments. This review summarizes representative advances over the past 5\u2009years in the molecular design of NTR\u2010responsive probes, with emphasis on recognition motifs, signal transduction strategies, and structure\u2010function relationships that determine selectivity and sensitivity. Disease\u2010oriented applications in cancer, bacterial infections, and other hypoxia\u2010associated disorders\u2014including myocardial ischemia, inflammatory bowel disease, pulmonary fibrosis, and infertility\u2014are discussed. Finally, current challenges and future opportunities are outlined to guide the development of next\u2010generation NTR\u2010responsive probes for high\u2010fidelity imaging and precision theranostic applications.<\/jats:p>","DOI":"10.1002\/cmdc.70323","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T22:20:03Z","timestamp":1780006803000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Nitroreductase\u2010Activated Fluorescent Probes: From Molecular Design to Disease Diagnosis"],"prefix":"10.1002","volume":"21","author":[{"given":"Weiqiang","family":"Ji","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Engineering and Key Laboratory of Structure\u2010Based Drug Design &amp; Discovery (Ministry of Education) Shenyang Pharmaceutical University  Shenyang China"},{"name":"Institute of Materia Medica Chinese Academy of Medical Sciences &amp; Peking Union Medical 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