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

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