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Life sciences · Journal article
Biosensors · September 27, 2026
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Hypoxia is a hallmark of numerous pathological conditions, such as cancer, drug-induced liver injury, and rheumatoid arthritis. Given the contrast in oxygen levels between pathological and normal tissues, hypoxia-activated prodrugs have been developed by incorporating hypoxia-responsive groups to achieve targeted therapy while minimizing toxicity to normal cells. Recently, the integration of drug delivery or activation (including triggered release) with fluorescence imaging has emerged as a promising strategy in prodrug design, enabling self-reporting of drug processes and facilitating preclinical evaluation of prodrug performance. This review provides a comprehensive overview of hypoxia-responsive fluorescent prodrugs capable of self-reporting drug delivery or activation/release via fluorescence readouts. We summarize recent advancements in such prodrugs, focusing on design strategies, drug release or activation mechanisms, fluorescence signal modulation, and biomedical applications, especially in cancer treatment. Furthermore, we discuss current challenges and future perspectives for hypoxia-responsive fluorescent prodrugs, as well as potential directions for the development of the next generation of hypoxia-responsive prodrugs.