Prominent Imaging for Differentiating Severity of Drug-Induced Liver Injury by an Esterase Activatable Near-Infrared Fluorescent Probe

Efficient imaging and differentiation of the severity of drug-induced liver injury (DILI) under diabetic conditions are crucial for preclinical drug safety evaluation. However, due to the absence of robust and distinctive parameters, most of the reported fluorescence probes fail to provide prominent imaging for differentiating severity of DILI during the progression of diabetes. Herein, a novel NIR fluorescent probe (WE) with high sensitivity toward esterase activity is developed, underscoring its potential for differentiating the severity of DILI from diabetes-induced hepatotoxicity. Inspiringly, probe WE can clearly differentiate between acetaminophen-induced DILI and diabetes-aggravated DILI by a significantly reduced fluorescence signal, resulting from ROS-mediated esterase inactivation and decreased esterase levels associated with synergistic liver dysfunction. This study not only extends the fluorescence probe’s capability for differential imaging from the liver injury microenvironment to chronic hepatopathy but also provides an additional dimension for differentially elucidating the pathological progression of disease-associated DILI.