A viscosity-responsive mitochondria-targeting probe for rapid imaging of fatty liver disease†

Fatty liver disease (FLD) is a leading cause of chronic liver disease worldwide, yet current diagnostic methods remain limited by low sensitivity, poor accuracy, and prolonged detection times. Recent studies have linked liver viscosity, particularly mitochondrial viscosity variations, to the progression of FLD, highlighting the need for a rapid and noninvasive viscosity-sensitive imaging tool. Herein, we present a viscosity-responsive fluorescent probe ZLCN, designed for rapid real-time imaging of fatty liver disease. ZLCN integrates an acrylonitrile rotor for viscosity sensing and a pyridine moiety for selective mitochondrial localization, enabling precise detection of viscosity alterations at the subcellular level. The probe exhibits strong fluorescence in high-viscosity environments due to restricted intramolecular rotation. ZLCN exhibits excellent viscosity responsiveness, effectively distinguishing normal and cancerous liver cells based on viscosity differences in vitro. Furthermore, it differentiates AML12 cells with varying viscosity levels, demonstrating its capability to monitor viscosity changes. In fatty liver models, ZLCN could produce intense fluorescence signals in fatty liver tissues and enabled rapid viscosity detection within 30 minutes, demonstrating a significant improvement over conventional imaging technique. These findings establish ZLCN as a promising tool for real-time mitochondrial viscosity monitoring, offering new avenues for early diagnosis and therapeutic assessment of viscosity-related liver diseases.