A polarity-sensitive fluorescent probe for targeted lipid droplets imaging and in vivo visualization of non-alcoholic fatty liver disease.

Lipid droplets (LDs) polarity and abundance are closely associated with pathological processes involving abnormal lipid metabolism. Excessive LDs accumulation in hepatocytes results in hepatic lipid deposition and the onset of non-alcoholic fatty liver disease (NAFLD). Consequently, monitoring alterations in LDs quantity and polarity is critically important for both biomedical research and the clinical diagnosis of NAFLD. However, developing LDs-specific fluorescent probes that integrate high polarity sensitivity with bright emission suitable for in vivo liver imaging remains a considerable challenge. Herein, we designed and synthesized four D-π-A structured compounds (FPLD-1 to FPLD-4) and systematically assessed their polarity sensitivity. Among them, FPLD-2 exhibited exceptional polarity sensitivity that is independent of solvent viscosity, along with strong fluorescence signal and a large Stokes shift. Cellular studies revealed that FPLD-2 specifically labels LDs and enables real-time monitoring of their dynamics. Moreover, FPLD-2 generated selective fluorescence signals in the livers of NAFLD mouse models and clearly delineated LDs in tissue sections, thereby enabling sensitive visualization of lipid accumulation in vivo. These results highlight FPLD-2 as a promising probe for investigating LDs-related physiological and pathological processes in NAFLD.