{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:42:10Z","timestamp":1792784530726,"version":"4.5.0"},"reference-count":46,"publisher":"American Chemical Society (ACS)","issue":"41","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2025JJ50125"],"award-info":[{"award-number":["2025JJ50125"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scientific Research Fund of Hunan Provincial Education Department","award":["24B0456"],"award-info":[{"award-number":["24B0456"]}],"id":[{"id":"https:\/\/ror.org\/026meb765","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Drug-induced liver injury (DILI) is a frequent clinical condition in which hepatocyte ferroptosis serves as a core pathological mechanism, leading to critical alterations in the mitochondrial microenvironment, including viscosity. However, visualizing mitochondrial viscosity changes in real time during ferroptosis-driven DILI remains technically challenging. Herein, we report XT-TPE, a mitochondrion-targeted near-infrared (NIR) \u201cturn-on\u201d viscosity probe based on a tetraphenylethylene (TPE)-xanthene hybrid. This probe gives a remarkable 129-fold fluorescence increase in high-viscosity media with an outstanding linear relationship (R2 &amp;gt; 0.999). The probe displays low cytotoxicity toward hepatocytes, excellent mitochondrial colocalization (Pearson\u2019s coefficient: 0.916), and enables sensitive monitoring of viscosity fluctuations during ferroptosis-mediated DILI both in vitro and in vivo. Using this probe, we screened 14 redox-active compounds and identified N-acetylcysteine (NAC) and ferrostatin-1 (Fer-1) as strong inhibitors of ferroptosis-driven DILI. In acetaminophen-induced DILI mouse models, XT-TPE enables noninvasive hepatic viscosity imaging and confirms the therapeutic efficacy of NAC and Fer-1. This work provides a reliable molecular tool for ferroptosis-related viscosity imaging and establishes a new strategy for anti-DILI drug screening.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c04129","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:02:21Z","timestamp":1790240541000},"page":"29616-29626","source":"Crossref","is-referenced-by-count":0,"title":["Real-Time Monitoring\nFerroptosis-Mediated Drug-Induced\nLiver Injury Using a Near-Infrared Mitochondrial Viscosity Probe"],"prefix":"10.1021","volume":"98","author":[{"given":"Ben","family":"Liu","sequence":"first","affiliation":[{"name":"Hunan University of Science and Technology , , ,","place":["Xiangtan, P. R. China, 411201"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwu","family":"Qiu","sequence":"additional","affiliation":[{"name":"Hunan University of Science and Technology , , ,","place":["Xiangtan, P. R. China, 411201"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"He","sequence":"additional","affiliation":[{"name":"Hunan University of Science and Technology , , ,","place":["Xiangtan, P. R. China, 411201"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4543-684X","authenticated-orcid":true,"given":"Yi","family":"Li","sequence":"additional","affiliation":[{"name":"Hunan University of Science and Technology , , ,","place":["Xiangtan, P. R. China, 411201"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"2026102006570943700_cit1","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.ejim.2021.10.035","article-title":"Drug-induced liver injury: Pathogenesis, epidemiology,\nclinical features, and practical management","volume":"97","author":"Bjo\u0308rnsson","year":"2022","journal-title":"Eur. J. Int. Med."},{"key":"2026102006570943700_cit2","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1097\/HEP.0000000000000628","article-title":"An entropy weight method to integrate\nbig omics and mechanistically evaluate DILI","volume":"79","author":"Jin","year":"2024","journal-title":"Hepatology"},{"key":"2026102006570943700_cit3","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.4254\/wjh.v13.i11.1688","article-title":"Abnormal liver enzymes: A review for clinicians","volume":"13","author":"Kalas","year":"2021","journal-title":"World J. Hepatol."},{"key":"2026102006570943700_cit4","doi-asserted-by":"publisher","first-page":"2401","DOI":"10.1016\/j.cell.2022.06.003","article-title":"Ferroptosis\nturns 10: Emerging mechanisms, physiological functions, and therapeutic\napplications","volume":"185","author":"Stockwell","year":"2022","journal-title":"Cell"},{"key":"2026102006570943700_cit5","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102892","article-title":"Differences\nin hepatocellular iron metabolism underlie sexual dimorphism in hepatocyte\nferroptosis","volume":"67","author":"Tao","year":"2023","journal-title":"Redox Biol."},{"key":"2026102006570943700_cit6","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1038\/s41420-021-00660-4","article-title":"Ferroptosis in liver\ndisease: new insights into disease\nmechanisms","volume":"7","author":"Wu","year":"2021","journal-title":"Cell Death Discovery"},{"key":"2026102006570943700_cit7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2023.114771","article-title":"Ferroptosis mediates\ndecabromodiphenyl ether-induced liver damage and inflammation","volume":"255","author":"Wang","year":"2023","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"2026102006570943700_cit8","doi-asserted-by":"publisher","DOI":"10.1016\/j.snb.2025.138985","article-title":"Revealing a close link\nbetween ferroptosis and drug-induced liver injury with dual-site NIR\nratiometric fluorescent probe for mitochondrial peroxynitrite","volume":"448","author":"Lu","year":"2026","journal-title":"Sens. Actuators, B"},{"key":"2026102006570943700_cit9","doi-asserted-by":"publisher","DOI":"10.1016\/j.saa.2024.125486","article-title":"Construction of a novel NIR-emissive rhodamine derivative\nfor monitoring mitochondrial viscosity in ferroptosis","volume":"328","author":"Liu","year":"2025","journal-title":"Spectrochim Acta, Part A"},{"key":"2026102006570943700_cit10","doi-asserted-by":"publisher","DOI":"10.1016\/j.snb.2021.130862","article-title":"Dual-responsive\nfluorescent probe for imaging NAD(P)H and mitochondrial viscosity\nand its application in cancer cell ferroptosis","volume":"350","author":"Wei","year":"2022","journal-title":"Sens. Actuators, B"},{"key":"2026102006570943700_cit11","doi-asserted-by":"publisher","DOI":"10.1016\/j.microc.2023.109010","article-title":"Visualizing mitochondrial\nviscosity during ferroptosis by using a solvatochromic effect-decreased\nhemicyanine probe","volume":"193","author":"Liu","year":"2023","journal-title":"Microchem. J."},{"key":"2026102006570943700_cit12","doi-asserted-by":"publisher","first-page":"17857","DOI":"10.1021\/acs.analchem.5c03499","article-title":"Reversible\nNIR Ratiometric Probe for Monitoring Redox Homeostasis in Lipid Droplets\nduring Ferroptosis-Driven Liver Injury","volume":"97","author":"Li","year":"2025","journal-title":"Anal.\nChem."},{"key":"2026102006570943700_cit13","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202510425","article-title":"Investigating Mitochondrial Viscosity in Ferroptosis-Mediated Drug-Induced\nLiver Injury using a Double-Targeted Strategy","volume":"13","author":"Zhou","year":"2026","journal-title":"Adv. Sci."},{"key":"2026102006570943700_cit14","doi-asserted-by":"publisher","DOI":"10.1016\/j.dyepig.2024.112102","article-title":"\u201cThree-key-and-lock\u201d\nnear-infrared fluorescent probe for dual-channel tracking ONOO\u2013\nin mitochondria and viscosity in lysosomes in ferroptosis and drug-induced\nliver injury","volume":"225","author":"Liu","year":"2024","journal-title":"Dyes Pigm."},{"key":"2026102006570943700_cit15","doi-asserted-by":"publisher","first-page":"1738","DOI":"10.1021\/acs.chemrev.3c00573","article-title":"Design and\nApplication of Fluorescent Probes to Detect Cellular Physical Microenvironments","volume":"124","author":"Ma","year":"2024","journal-title":"Chem. 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Chem."},{"key":"2026102006570943700_cit19","doi-asserted-by":"publisher","DOI":"10.1016\/j.cclet.2025.110962","article-title":"A dual-targeted near-infrared\nfluorescence lifetime probe for detecting viscosity heterogeneity\nin arthritic mice","volume":"36","author":"Wang","year":"2025","journal-title":"Chin. Chem. Lett."},{"key":"2026102006570943700_cit20","doi-asserted-by":"publisher","first-page":"3641","DOI":"10.1016\/j.cclet.2021.04.035","article-title":"Visualization of endoplasmic\nreticulum viscosity in the liver of mice with nonalcoholic fatty liver\ndisease by a near-infrared fluorescence probe","volume":"32","author":"Zhou","year":"2021","journal-title":"Chin. Chem. Lett."},{"key":"2026102006570943700_cit21","doi-asserted-by":"publisher","first-page":"4228","DOI":"10.1039\/C4CS00325J","article-title":"Biosensing\nby luminogens\nwith aggregation-induced emission characteristics","volume":"44","author":"Kwok","year":"2015","journal-title":"Chem. Soc. 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Chem.\nRes."},{"key":"2026102006570943700_cit25","doi-asserted-by":"publisher","DOI":"10.1016\/j.snb.2025.138754","article-title":"Embedding linear rotors\ninto cyanine scaffolds for photostable, viscosity-responsive AIE probes\ntoward pathology-relevant biological imaging","volume":"446","author":"Liu","year":"2026","journal-title":"Sens. Actuators, B"},{"key":"2026102006570943700_cit26","doi-asserted-by":"publisher","DOI":"10.1016\/j.saa.2023.123329","article-title":"A novel near-infrared fluorescent probe for ultrasensitive and visual\ndetection of mitochondrial viscosity","volume":"304","author":"Liu","year":"2024","journal-title":"Spectrochim\nActa, Part A"},{"key":"2026102006570943700_cit27","doi-asserted-by":"publisher","DOI":"10.1016\/j.trac.2026.118675","article-title":"Chemical design of\norganelle-targeting molecular rotors for intracellular\nviscosity imaging","volume":"197","author":"Han","year":"2026","journal-title":"TrAC, Trends Anal. Chem."},{"key":"2026102006570943700_cit28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cclet.2025.111495","article-title":"Viscosity responsiveness\nof excited-state dynamics\nin aggregated-induced emission luminogens","volume":"36","author":"Tanaka","year":"2025","journal-title":"Chin.\nChem. Lett."},{"key":"2026102006570943700_cit29","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2026.135244","article-title":"A molecular\nrotor-based NIR probe with large stokes shift for highly sensitive\ntracking of mitochondrial viscosity in live tumors","volume":"195","author":"Wang","year":"2026","journal-title":"Tetrahedron"},{"key":"2026102006570943700_cit30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphotochem.2026.117253","article-title":"Carbazole\/triphenylamine-based red-emitting\nprobes for mitochondrial viscosity imaging and tumor visualization","volume":"478","author":"Wan","year":"2026","journal-title":"J. Photochem. Photobiol., A"},{"key":"2026102006570943700_cit31","doi-asserted-by":"publisher","DOI":"10.1016\/j.saa.2025.127062","article-title":"A novel mitochondria-targeted\nred-light emission fluorescent probe for monitoring the viscosity\nin drug-induced liver injury","volume":"348","author":"Zhang","year":"2026","journal-title":"Spectrochim Acta,\nPart A"},{"key":"2026102006570943700_cit32","doi-asserted-by":"publisher","DOI":"10.1016\/j.saa.2025.127424","article-title":"An ultralow-concentration, red-emissive dual-responsive\nfluorescent probe for real-time mitochondrial viscosity\/polarity imaging","volume":"350","author":"Yu","year":"2026","journal-title":"Spectrochim Acta, Part A"},{"key":"2026102006570943700_cit33","doi-asserted-by":"publisher","first-page":"4037","DOI":"10.1039\/D6CC00108D","article-title":"A multi-rotor near-infrared\nprobe for high-sensitivity imaging of mitochondrial viscosity in epilepsy","volume":"62","author":"Lu","year":"2026","journal-title":"Chem. Commun."},{"key":"2026102006570943700_cit34","doi-asserted-by":"publisher","first-page":"3921","DOI":"10.1039\/D0SC05937D","article-title":"Fluorescent probe for the imaging\nof superoxide and peroxynitrite during drug-induced liver injury","volume":"12","author":"Wu","year":"2021","journal-title":"Chem. Sci."},{"key":"2026102006570943700_cit35","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1002\/jcc.22885","article-title":"Multiwfn: a multifunctional wavefunction analyzer","volume":"33","author":"Lu","year":"2012","journal-title":"J. Comput. Chem."},{"key":"2026102006570943700_cit36","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2023.340813","article-title":"A near-infrared fluorescent probe\nfor monitoring abnormal mitochondrial viscosity in cancer and fatty-liver\nmice model","volume":"1242","author":"Chao","year":"2023","journal-title":"Anal. Chim. Acta"},{"key":"2026102006570943700_cit37","doi-asserted-by":"publisher","first-page":"2072","DOI":"10.1021\/acs.analchem.0c03803","article-title":"Noninvasive\nCancer Diagnosis In Vivo\nBased on a Viscosity-Activated Near-Infrared Fluorescent Probe","volume":"93","author":"Yin","year":"2021","journal-title":"Anal. Chem."},{"key":"2026102006570943700_cit38","doi-asserted-by":"publisher","first-page":"7611","DOI":"10.1021\/acs.analchem.3c00436","article-title":"Rational Design of\nMMP-Independent Near-Infrared Fluorescent Probes for Accurately Monitoring\nMitochondrial Viscosity","volume":"95","author":"Wu","year":"2023","journal-title":"Anal. Chem."},{"key":"2026102006570943700_cit39","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2021.111626","article-title":"Mitochondria-targeted\nphosphorescent cyclometalated iridium(III) complex for bioimaging\nof H2S","volume":"226","author":"Liu","year":"2022","journal-title":"J. Inorg. Biochem."},{"key":"2026102006570943700_cit40","doi-asserted-by":"publisher","first-page":"9001","DOI":"10.1021\/jacs.4c17092","article-title":"Advances in Organic\nSmall Molecule-Based Fluorescent Probes for Precision Detection of\nLiver Diseases: A Perspective on Emerging Trends and Challenges","volume":"147","author":"Wu","year":"2025","journal-title":"J. Am. Chem. Soc."},{"key":"2026102006570943700_cit41","doi-asserted-by":"publisher","first-page":"4570","DOI":"10.1021\/acs.analchem.3c05430","article-title":"Reversible\nDual Fluorescence-Lifetime Imaging of Mitochondrial GSH and Microviscosity:\nReal-Time Evaluation of Ferroptosis Status","volume":"96","author":"Wang","year":"2024","journal-title":"Anal. Chem."},{"key":"2026102006570943700_cit42","doi-asserted-by":"publisher","DOI":"10.1016\/j.dyepig.2023.111424","article-title":"Real-time monitoring\nviscosity during ferroptosis with a novel mitochondria-specific fluorescent\nprobe","volume":"217","author":"Zheng","year":"2023","journal-title":"Dyes Pigm."},{"key":"2026102006570943700_cit43","doi-asserted-by":"publisher","first-page":"6155","DOI":"10.1021\/acs.analchem.4c06840","article-title":"Time Series\nImaging the Mitochondrial Microenvironment and Its Interactions\nwith Lysosomes during Ferroptosis","volume":"97","author":"Shao","year":"2025","journal-title":"Anal. Chem."},{"key":"2026102006570943700_cit44","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1038\/s41418-022-00941-0","article-title":"The multifaceted role\nof ferroptosis in liver disease","volume":"29","author":"Chen","year":"2022","journal-title":"Cell Death\nDiffer."},{"key":"2026102006570943700_cit45","doi-asserted-by":"publisher","DOI":"10.1016\/j.snb.2025.137887","article-title":"Innovative two-dimensional\nfluorescent probe of viscosity and ONOO- for high-throughput screening\nof antioxidant drugs and its application in epilepsy","volume":"440","author":"Zhan","year":"2025","journal-title":"Sens. Actuators, B"},{"key":"2026102006570943700_cit46","doi-asserted-by":"publisher","first-page":"9493","DOI":"10.1021\/acs.analchem.9b05826","article-title":"Visual High-Throughput\nScreening\nfor Developing a Fatty Acid Amide Hydrolase Natural Inhibitor Based\non an Enzyme-Activated Fluorescent Probe","volume":"92","author":"Tian","year":"2020","journal-title":"Anal.\nChem."}],"container-title":["Analytical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.analchem.6c04129","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/41\/29616\/68633936\/acs.analchem.6c04129.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/41\/29616\/68633936\/acs.analchem.6c04129.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:09:30Z","timestamp":1792494570000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancham\/article\/98\/41\/29616\/5437409\/Real-Time-Monitoring-Ferroptosis-Mediated-Drug"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":46,"journal-issue":{"issue":"41","published-online":{"date-parts":[[2026,9,24]]},"published-print":{"date-parts":[[2026,10,20]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.analchem.6c04129","relation":{},"ISSN":["0003-2700","1520-6882"],"issn-type":[{"value":"0003-2700","type":"print"},{"value":"1520-6882","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]}}}