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. SML 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 SML probe to be effectively utilized for the rapid monitoring nanoscale upregulation of H₂O₂ during DILI and hepatic fibrosis, thus providing SML with the capability to screen for effective therapeutic candidates.