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Due to the widespread use of drugs, drug-induced liver injury (DILI) has become a global liver disease that seriously endangers human health. The pathological mechanism of DILI is complex, and the mitochondrial polarity changes in liver tissues during DILI are not yet clear. For this purpose, a polarity-sensitive mitochondria-targeting near-infrared (NIR) fluorescent probe (named Mito-PDSM) was synthesized in this work. Mito-PDSM is based on dicyanomethylene-4H-benzothiopyran, and a pyridinium unit was introduced, which not only prolongs conjugation but also increases water solubility and enables Mito-PDSM to target mitochondria. Mito-PDSM features NIR fluorescence (\u03bbem &amp;gt; 730 nm), large Stokes shift (&amp;gt;135 nm), specific mitochondria-targeting, and excellent polarity sensitivity, enabling it to sensitively detect changes in mitochondrial polarity. With these characteristics, Mito-PDSM successfully distinguishes cancer cells from normal cells, revealing that cancer cell mitochondria have lower polarity. By constructing a mouse DILI model for in vivo imaging, it was found that Mito-PDSM targets the liver and displays significantly brighter fluorescence in the DILI mouse liver, revealing a decrease in liver tissue polarity during DILI. Overall, this work provides a valuable new method for detecting mitochondrial polarity and related diseases such as DILI.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c03493","type":"journal-article","created":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:43:40Z","timestamp":1783730620000},"page":"21892-21900","source":"Crossref","is-referenced-by-count":0,"title":["Near-Infrared\nPolarity-Sensitive Fluorescent Probe\nfor Distinguishing Normal and Cancer Cells and Imaging Mitochondrial\nPolarity Changes during Drug-Induced Liver Injury"],"prefix":"10.1021","volume":"98","author":[{"given":"Meiling","family":"Wang","sequence":"first","affiliation":[{"name":"Central China Normal University , , 152 Luoyu Road , ,","place":["Wuhan, China, 430079"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhao","sequence":"additional","affiliation":[{"name":"Central China Normal University , , 152 Luoyu Road , ,","place":["Wuhan, China, 430079"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanting","family":"Wang","sequence":"additional","affiliation":[{"name":"Central China Normal University , , 152 Luoyu Road , ,","place":["Wuhan, China, 430079"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijia","family":"Liu","sequence":"additional","affiliation":[{"name":"Central China Normal University , , 152 Luoyu Road , ,","place":["Wuhan, China, 430079"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Central China Normal University , , 152 Luoyu Road , ,","place":["Wuhan, China, 430079"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2548-7284","authenticated-orcid":true,"given":"Guoqiang","family":"Feng","sequence":"additional","affiliation":[{"name":"Central China Normal University , , 152 Luoyu Road , ,","place":["Wuhan, China, 430079"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"2026072808082131800_cit1","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1016\/j.cell.2012.02.035","article-title":"Mitochondria: In sickness and in health","volume":"148","author":"Nunnari","year":"2012","journal-title":"Cell"},{"key":"2026072808082131800_cit2","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1038\/s41556-024-01429-4","article-title":"Mitochondria\nand cell death","volume":"26","author":"Glover","year":"2024","journal-title":"Nat. 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