Probing mitochondrial peroxynitrite biogenesis by a N-morpholinoarylimine-based iridium(III) complex in drug-induced liver cells
Peroxynitrite (ONOO−), a strong oxidizing agent, has an important function in the pathogenesis of various diseases, including cardiovascular, inflammatory and neurodegenerative diseases. Specifically, mitochondrial ONOO− exacerbates liver injury by driving oxidative/nitrative stress and mitochondria...
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Elsevier
2025-10-01
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| Series: | Redox Biology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231725003180 |
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| author | Lingtan Kong Ling Wang Zixi Zhang Liuqi Ye Daniel Shiu-Hin Chan Chun-Yuen Wong Jing Wang Chung-Hang Leung Wanhe Wang |
| author_facet | Lingtan Kong Ling Wang Zixi Zhang Liuqi Ye Daniel Shiu-Hin Chan Chun-Yuen Wong Jing Wang Chung-Hang Leung Wanhe Wang |
| author_sort | Lingtan Kong |
| collection | DOAJ |
| description | Peroxynitrite (ONOO−), a strong oxidizing agent, has an important function in the pathogenesis of various diseases, including cardiovascular, inflammatory and neurodegenerative diseases. Specifically, mitochondrial ONOO− exacerbates liver injury by driving oxidative/nitrative stress and mitochondrial dysfunction, ultimately triggering dual apoptotic-necrotic hepatocyte death pathways. ONOO− and its functions have been widely studied by fluorescence imaging probes, owing to their strong sensitivity, non-invasiveness, and real-time ability. However, existing probes are heavily constrained by interference from other reactive species. Herein, we describe a luminescent iridium(III) complex (1) with an N-morpholinoarylimine moiety as the recognition site for ONOO− for imaging mitochondrial ONOO−. The probe shows high luminescence response to ONOO− in aqueous buffer, with a luminescence enhancement of 27-fold at 100 μM ONOO− and a limit of detection (LOD) of 0.65 μM, as well as high selectivity over other reactive species. Furthermore, the probe can sense both exogenous and endogenous mitochondrial ONOO−. Further experiments demonstrated it could visualize exogenous ONOO− in 3D multicellular tumor spheroids (MCTSs) and unmask endogenous ONOO− production through an NADPH oxidase 4 (NOX-4)-mediated pathway in drug-induced liver cells. This work demonstrates the potential of this strategy for developing imaging tools for probing the pathological roles of subcellar ONOO− and diagnosing liver injury in the clinic. |
| format | Article |
| id | doaj-art-4fdde4250dbf4aa1bd23a3a620cfd87b |
| institution | Kabale University |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-10-01 |
| publisher | Elsevier |
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| series | Redox Biology |
| spelling | doaj-art-4fdde4250dbf4aa1bd23a3a620cfd87b2025-08-20T03:40:54ZengElsevierRedox Biology2213-23172025-10-018610380510.1016/j.redox.2025.103805Probing mitochondrial peroxynitrite biogenesis by a N-morpholinoarylimine-based iridium(III) complex in drug-induced liver cellsLingtan Kong0Ling Wang1Zixi Zhang2Liuqi Ye3Daniel Shiu-Hin Chan4Chun-Yuen Wong5Jing Wang6Chung-Hang Leung7Wanhe Wang8Institute of Medical Research, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an, Shaanxi, 710072, ChinaThe State Key Laboratory of Mechanism and Quality of Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, MacaoInstitute of Medical Research, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an, Shaanxi, 710072, ChinaThe State Key Laboratory of Mechanism and Quality of Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, MacaoDepartment of Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong SARDepartment of Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong SAR; Corresponding author. Department of Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong SAR.Institute of Medical Research, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an, Shaanxi, 710072, China; Research & Development Institute of Northwestern Polytechnical University in Shenzhen, 45 South Gaoxin Road, Shenzhen, 518057, China; Corresponding author. Institute of Medical Research, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an, Shaanxi, 710072, China.The State Key Laboratory of Mechanism and Quality of Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao; Corresponding author. The State Key Laboratory of Mechanism and Quality of Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao.Institute of Medical Research, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an, Shaanxi, 710072, China; Research & Development Institute of Northwestern Polytechnical University in Shenzhen, 45 South Gaoxin Road, Shenzhen, 518057, China; Corresponding author. Institute of Medical Research, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an, Shaanxi, 710072, China.Peroxynitrite (ONOO−), a strong oxidizing agent, has an important function in the pathogenesis of various diseases, including cardiovascular, inflammatory and neurodegenerative diseases. Specifically, mitochondrial ONOO− exacerbates liver injury by driving oxidative/nitrative stress and mitochondrial dysfunction, ultimately triggering dual apoptotic-necrotic hepatocyte death pathways. ONOO− and its functions have been widely studied by fluorescence imaging probes, owing to their strong sensitivity, non-invasiveness, and real-time ability. However, existing probes are heavily constrained by interference from other reactive species. Herein, we describe a luminescent iridium(III) complex (1) with an N-morpholinoarylimine moiety as the recognition site for ONOO− for imaging mitochondrial ONOO−. The probe shows high luminescence response to ONOO− in aqueous buffer, with a luminescence enhancement of 27-fold at 100 μM ONOO− and a limit of detection (LOD) of 0.65 μM, as well as high selectivity over other reactive species. Furthermore, the probe can sense both exogenous and endogenous mitochondrial ONOO−. Further experiments demonstrated it could visualize exogenous ONOO− in 3D multicellular tumor spheroids (MCTSs) and unmask endogenous ONOO− production through an NADPH oxidase 4 (NOX-4)-mediated pathway in drug-induced liver cells. This work demonstrates the potential of this strategy for developing imaging tools for probing the pathological roles of subcellar ONOO− and diagnosing liver injury in the clinic.http://www.sciencedirect.com/science/article/pii/S2213231725003180 |
| spellingShingle | Lingtan Kong Ling Wang Zixi Zhang Liuqi Ye Daniel Shiu-Hin Chan Chun-Yuen Wong Jing Wang Chung-Hang Leung Wanhe Wang Probing mitochondrial peroxynitrite biogenesis by a N-morpholinoarylimine-based iridium(III) complex in drug-induced liver cells Redox Biology |
| title | Probing mitochondrial peroxynitrite biogenesis by a N-morpholinoarylimine-based iridium(III) complex in drug-induced liver cells |
| title_full | Probing mitochondrial peroxynitrite biogenesis by a N-morpholinoarylimine-based iridium(III) complex in drug-induced liver cells |
| title_fullStr | Probing mitochondrial peroxynitrite biogenesis by a N-morpholinoarylimine-based iridium(III) complex in drug-induced liver cells |
| title_full_unstemmed | Probing mitochondrial peroxynitrite biogenesis by a N-morpholinoarylimine-based iridium(III) complex in drug-induced liver cells |
| title_short | Probing mitochondrial peroxynitrite biogenesis by a N-morpholinoarylimine-based iridium(III) complex in drug-induced liver cells |
| title_sort | probing mitochondrial peroxynitrite biogenesis by a n morpholinoarylimine based iridium iii complex in drug induced liver cells |
| url | http://www.sciencedirect.com/science/article/pii/S2213231725003180 |
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