A rhodamine-coordinated iridium complex to overcome cisplatin-resistant cancer via regulating mitochondrial function triggered apoptosis and ferroptosis
Modulating mitochondrial activity to regulate cancer cell homeostatic recycling presents a promising approach to overcome tumor resistance. Consequently, there is an urgent need for novel mitochondria-targeting agents and innovative strategies. We have developed [((η5-Cp∗)Ir(rhod)]2+2PF6− (Ir-rhod),...
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Elsevier
2025-04-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231725000497 |
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| author | Juanjuan Li Guibin Gao Wenrui Ouyang Jinkun Huang Hongxing Liu Jin Li |
| author_facet | Juanjuan Li Guibin Gao Wenrui Ouyang Jinkun Huang Hongxing Liu Jin Li |
| author_sort | Juanjuan Li |
| collection | DOAJ |
| description | Modulating mitochondrial activity to regulate cancer cell homeostatic recycling presents a promising approach to overcome tumor resistance. Consequently, there is an urgent need for novel mitochondria-targeting agents and innovative strategies. We have developed [((η5-Cp∗)Ir(rhod)]2+2PF6− (Ir-rhod), a new mitochondria-targeted iridium complex that exhibits greater cytotoxicity towards A549R (cisplatin-resistant human lung cancer) cells compared to the ligand rhod. Ir-rhod's mitochondrial targeting ability stems from both rhodamine's inherent mitochondrial affinity and the complex's positive bivalent nature. The positively charged Ir-rhod enters cells and is drawn to mitochondria due to the high transmembrane potential in tumor cells. Notably, rhodamine enables real-time observation of Ir-rhod's dynamic distribution in vivo. Ir-rhod influences mitochondrial function, triggering tumor cell ferroptosis and apoptosis by modulating ACSL4 and GPX4. The targeting effect of Ir-rhod reduces its systemic toxicity in vivo, enhancing its biosafety profile. To our knowledge, Ir-rhod is an effective mitochondria-targeted Ir complex capable of inducing tumor cell death by disrupting mitochondrial function, offering a potent strategy to suppress cisplatin resistance in non-small cell lung cancer. |
| format | Article |
| id | doaj-art-a394c3d6f6d2420ba652aba929df0607 |
| institution | DOAJ |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-a394c3d6f6d2420ba652aba929df06072025-08-20T03:02:56ZengElsevierRedox Biology2213-23172025-04-018110353610.1016/j.redox.2025.103536A rhodamine-coordinated iridium complex to overcome cisplatin-resistant cancer via regulating mitochondrial function triggered apoptosis and ferroptosisJuanjuan Li0Guibin Gao1Wenrui Ouyang2Jinkun Huang3Hongxing Liu4Jin Li5Department of Urology, Guangzhou Institute of Urology, Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510230, ChinaGuangdong Provincial Key Laboratory of Allergy & Immunology the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510230, ChinaDepartment of Urology, Guangzhou Institute of Urology, Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510230, ChinaDepartment of Urology, Guangzhou Institute of Urology, Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510230, ChinaDepartment of Urology, Guangzhou Institute of Urology, Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510230, China; Corresponding author.Department of Oncology, The Key Laboratory of Advanced Interdisciplinary Studies, The State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510163, China; Corresponding author.Modulating mitochondrial activity to regulate cancer cell homeostatic recycling presents a promising approach to overcome tumor resistance. Consequently, there is an urgent need for novel mitochondria-targeting agents and innovative strategies. We have developed [((η5-Cp∗)Ir(rhod)]2+2PF6− (Ir-rhod), a new mitochondria-targeted iridium complex that exhibits greater cytotoxicity towards A549R (cisplatin-resistant human lung cancer) cells compared to the ligand rhod. Ir-rhod's mitochondrial targeting ability stems from both rhodamine's inherent mitochondrial affinity and the complex's positive bivalent nature. The positively charged Ir-rhod enters cells and is drawn to mitochondria due to the high transmembrane potential in tumor cells. Notably, rhodamine enables real-time observation of Ir-rhod's dynamic distribution in vivo. Ir-rhod influences mitochondrial function, triggering tumor cell ferroptosis and apoptosis by modulating ACSL4 and GPX4. The targeting effect of Ir-rhod reduces its systemic toxicity in vivo, enhancing its biosafety profile. To our knowledge, Ir-rhod is an effective mitochondria-targeted Ir complex capable of inducing tumor cell death by disrupting mitochondrial function, offering a potent strategy to suppress cisplatin resistance in non-small cell lung cancer.http://www.sciencedirect.com/science/article/pii/S2213231725000497Mitochondria-targetedIridium complexFerroptosisMitochondrial functionCisplatin-resistant non-small cell lung cancer |
| spellingShingle | Juanjuan Li Guibin Gao Wenrui Ouyang Jinkun Huang Hongxing Liu Jin Li A rhodamine-coordinated iridium complex to overcome cisplatin-resistant cancer via regulating mitochondrial function triggered apoptosis and ferroptosis Redox Biology Mitochondria-targeted Iridium complex Ferroptosis Mitochondrial function Cisplatin-resistant non-small cell lung cancer |
| title | A rhodamine-coordinated iridium complex to overcome cisplatin-resistant cancer via regulating mitochondrial function triggered apoptosis and ferroptosis |
| title_full | A rhodamine-coordinated iridium complex to overcome cisplatin-resistant cancer via regulating mitochondrial function triggered apoptosis and ferroptosis |
| title_fullStr | A rhodamine-coordinated iridium complex to overcome cisplatin-resistant cancer via regulating mitochondrial function triggered apoptosis and ferroptosis |
| title_full_unstemmed | A rhodamine-coordinated iridium complex to overcome cisplatin-resistant cancer via regulating mitochondrial function triggered apoptosis and ferroptosis |
| title_short | A rhodamine-coordinated iridium complex to overcome cisplatin-resistant cancer via regulating mitochondrial function triggered apoptosis and ferroptosis |
| title_sort | rhodamine coordinated iridium complex to overcome cisplatin resistant cancer via regulating mitochondrial function triggered apoptosis and ferroptosis |
| topic | Mitochondria-targeted Iridium complex Ferroptosis Mitochondrial function Cisplatin-resistant non-small cell lung cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2213231725000497 |
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