Mitochondria-Targetable Cyclometalated Iridium(III)\nComplex-Based Luminescence Probe for Monitoring and Assessing Treatment\nResponse of Ferroptosis-Mediated Hepatic Ischemia-Reperfusion Injury

Ferroptosis\nplays an essential role in the pathological progression\nof hepatic ischemia-reperfusion injury (HIRI), which is closely related\nto iron-dependent lipid peroxidation. Since mitochondria are thought\nto be the major site of reactive oxygen species (ROS) production and\niron storage, monitoring the variations of mitochondrial hypochlorous\nacid (HClO) (an important member of ROS) has important implications\nfor the assessment of ferroptosis status, as well as the formulation\nof treatment strategies for HIRI. However, reliable imaging tools\nfor the visualization of mitochondrial HClO and monitoring its dynamic\nchanges in ferroptosis-mediated HIRI are still lacking. Herein, in\nthis work, an HClO-activated near-infrared (NIR) cyclometalated iridium(III)\ncomplex-based probe, named NIR-Ir-HClO, was developed for the visual\nmonitoring of the mitochondrial HClO fluxes in ferroptosis-mediated\nHIRI. The newly prepared probe showed fast response (<30 s), good\nsensitivity, excellent selectivity, good cell biocompatibility, and\nsatisfactory mitochondrial-targeting performance, making it suitable\nfor accurate monitoring of mitochondrial HClO in living cells. Moreover,\nvisualization of the variations of mitochondrial HClO in ferroptosis-mediated\nHIRI and monitoring of the treatment response of ferroptosis-mediated\nHIRI to the ferroptosis inhibitors were achieved for the first time.\nAll these show that probe NIR-Ir-HClO can be utilized as a reliable\nimaging tool for revealing the pathological mechanism of mitochondrial\nHClO in ferroptosis-mediated HIRI, as well as for the formulation\nof new treatment strategies for HIRI.