Super-Resolution Mitochondrial Fluorescent Probe for Accurate Monitoring of Drug-Induced Liver Injury

Drug-induced liver injury (DILI) has emerged as an urgent clinical challenge. It is characterized by mitochondrial dysfunction in liver cells, which leads to abnormal changes in H₂O₂ levels within the mitochondria. Super-resolution imaging allows for the observation of the fine structure of mitochondria at the nanometer scale, potentially enabling the detection of mitochondrial H₂O₂ levels during DILI at the subcellular organelle level. Here, we report the design and synthesis of a novel H₂O₂-activated probe for the detection of mitochondrial H₂O₂ levels. <b>SML</b> is a near-infrared (NIR) fluorescent probe with a large Stokes shift (260 nm) and a sensing mechanism based on intramolecular charge transfer (ICT) switching. Super-resolution imaging of mitochondrial H₂O₂ was conducted using structured illumination microscopy (SIM). The improved accuracy in observing periods of mitochondrial dysfunction allows the <b>SML</b> probe to be effectively utilized for the rapid monitoring nanoscale upregulation of H₂O₂ during DILI and hepatic fibrosis, thus providing <b>SML</b> with the capability to screen for effective therapeutic candidates.