A novel mitochondria-targeted red-light emission fluorescent probe for monitoring the viscosity in drug-induced liver injury.

Drug-induced liver injury (DILI) remains a major challenge in clinical drug development and application. Hepatocyte dysfunction is central to its pathogenesis, with intracellular viscosity serving as an early biophysical marker of cellular state. Here, we reported the design and synthesis of probe CSQ, a mitochondria-targeted fluorescent probe comprising carbazole, thiophene, and quinolinium groups. CSQ enables highly specific and sensitive detection of intracellular viscosity, exhibiting a fluorescence enhancement of 107-fold in high-viscosity environments, along with excellent photostability and biocompatibility. In vitro, CSQ effectively monitored alterations in mitochondrial viscosity within an acetaminophen-induced DILI cell model. In vivo, it enabled visualization of aberrant mitochondrial viscosity in the liver of DILI mice, with the fluorescence intensity demonstrating a strong correlation with the extent of liver injury. These findings position CSQ as a reliable tool for the early diagnosis of DILI and for exploring its underlying mechanistic.