A red fluorescent probe for lipid droplet polarity sensitivity and identification of nonalcoholic fatty liver disease

The increasing prevalence of non-alcoholic fatty liver disease (NAFLD) has attracted widespread attention in recent years. As critical intracellular sites for energy storage, lipid droplets (LDs) have become one of the important biomarkers for early diagnosis of NAFLD. Therefore, a series of fluorescent probes (WL1-WL3) with D-π-A-D and D-π-A structures were designed and synthesized in this study. Photophysical property studies shown that all these probes are highly sensitive to polarity and insensitive to various analytes and pH changes. Among them, probe WL3 showed excellent optical properties, with an emission wavelength in the near-infrared region (>650 nm), a large Stokes shift, and a good linear correlation between fluorescence intensity and solvent polarity. Further biological results demonstrated that probe WL3 not only monitors alterations in the number and size of LDs, but also detects variations in the polarity of intracellular LDs and dynamically tracks LDs-related processes (LDs autophagy). In a NAFLD cell model, probe WL3 could effectively monitor the efficacy of metformin (Met) in the treatment of NAFLD. Furthermore, probe WL3 was able to clearly distinguish normal liver from NAFLD at both the tissue and organ level, demonstrating its promising potential for clinical potential.