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Nevertheless, mitochondrial function and membrane potential may be impaired in the occurrence and development of DILI, so accurately monitoring viscosity changes remains a difficult task. Considering the presence of high expression of mitochondrial uncoupling protein 2 (UCP2) in liver injury, a new near\u2010infrared fluorescent probe (named FTZ\u20102) is presented to investigate the tanglesome relationships between mitochondrial viscosity and ferroptosis\u2010mediated DILI by introducing a mitochondrial double\u2010targeted strategy that combined electrostatic reaction and probe\u2013protein docking. The newly synthetized FTZ\u20102 is highly selective to environmental viscosity in the presence of reactive species. Owing to its favorable cytotoxicity and mitochondrial localization characteristics, FTZ\u20102 is used to monitor viscosity variations in ferroptosis cells and ferroptosis\u2010mediated DILI mice. The reduction of fluorescence signals indicated that ferrostatin\u20101, glutathione, and N\u2010acetyl\u2010L\u2010cysteine can alleviate liver injury. Notably, the high expression of UCP2 is also discovered in the liver of ferroptosis mice and ferroptosis\u2010mediated DILI mice. Taken together, this work demonstrated a double\u2010targeted strategy for the early diagnosis and evaluation of liver injury through mitochondrial viscosity variations and contributed to the improvement of the therapeutic effect against liver injury.<\/jats:p>","DOI":"10.1002\/advs.202510425","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T11:24:16Z","timestamp":1765884256000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Investigating Mitochondrial Viscosity in Ferroptosis\u2010Mediated Drug\u2010Induced Liver Injury using a Double\u2010Targeted Strategy"],"prefix":"10.1002","volume":"13","author":[{"given":"Yongqing","family":"Zhou","sequence":"first","affiliation":[{"name":"School of Chemistry and Chemical Engineering University of Jinan  Jinan 250022 P. R. 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