A rhodamine-coordinated iridium complex to overcome cisplatin-resistant cancer via regulating mitochondrial function triggered apoptosis and ferroptosis

作者：Juanjuan Li, Juanjuan Li, Gui‐Bin Gao, Wenrui Ouyang, Jinkun Huang, Hongxing Liu, Jin Li, Jin Li · 发表于：Redox Biology · 年份：2025 · DOI：10.1016/j.redox.2025.103536 · 被引用次数：16 · 研究领域：Ferroptosis and cancer prognosis、Advanced biosensing and bioanalysis techniques、RNA modifications and cancer

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 [((η 5 -Cp∗)Ir(rhod)] 2+ 2PF 6 − ( 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. • Iridium complex Ir-rhod with rhodamine as the ligand, which possesses imaging and mitochondrial targeting capabilities. • The iridium complex Ir-rhod regulating mitochondrial function by...