An "enhanced PET"-based dual-positive charges fluorescent probe to detect hypochlorous acid for monitoring the drug-damaged liver.

Drug-induced liver injury (DILI) is an acute inflammatory condition that poses a serious threat to human health. Hypochlorous acid (HClO), a reactive oxygen species, has been identified as a key biomarker for monitoring the progression of DILI. Herein, we rationally designed a phenothiazine-based fluorescent probe, DMPTC, featuring a "dual-positive-charge" structure. This design leverages an "enhanced photoinduced electron transfer (PET)" effect to simultaneously achieve high response sensitivity to HClO and superior mitochondrial targeting capability. As anticipated, DMPTC demonstrated excellent performance in HClO detection, including a low detection limit (8.9 nM), high selectivity and anti-interference ability, and an enhanced fluorescence quantum yield (ΦF = 5.79). Benefiting from these advantages, DMPTC was successfully applied to quantify HClO levels in various real samples and to visualize fluctuations in both exogenous and endogenous HClO within the mitochondria of living cells and zebrafish. Moreover, the probe served as an effective tool for monitoring HClO generation in diverse pathological models, including inflammation, drug-induced liver injury, hyperglycemia, and ferroptosis. Crucially, DMPTC was further utilized to assess endogenous HClO production in a mouse model of liver injury.