An ICT + ESIPT synergistic NIR ratiometric probe for mitochondrial MAOs imaging in vivo and in vitro.

The liver is a vital metabolic and detoxification organ in the body, yet the diagnosis of drug-induced liver injury (DILI) remains challenging due to the limitations of traditional detection methods. Monoamine oxidases (MAOs), which are highly expressed on the mitochondrial membrane of hepatic tissues, are closely associated with DILI. In this study, a near-infrared ratiometric fluorescent probe Mito-1 was developed based on the intramolecular charge transfer (ICT) and excited-state intramolecular proton transfer (ESIPT) mechanisms. This probe could precisely target mitochondria, exhibiting high sensitivity (DL = 0.14 μg/mL), a wide linear detection range (10-150 μg/mL), excellent selectivity towards MAOs, and good biocompatibility. Cellular experiments confirmed its ability to distinguish MAO activity between normal and liver cancer cells. In an acetaminophen (APAP)-induced DILI zebrafish model, Mito-1 enabled in vivo dynamic visualization of MAO activity in hepatic tissues. Collectively, this work provides a novel visual tool for the early diagnosis of DILI and the mechanistic study of MAOs.