Polarity-sensitive fluorescent probe based on coumarin derivatives for imaging lipid droplets and diagnosis of non-alcoholic fatty liver

•Four compounds XOT1-XOT4 with different terminal groups were synthesized using triphenylamine and coumarin as the main substituents.•The fluorescence intensity of XOT1-XOT4 exhibited a good linear correlation with polarity.•Among them, XOT3 with ester group can effectively monitor changes in LDs polarity during apoptosis and ferroptosis process.•XOT3 could be effectively utilized for visualizing intracellular LDs without requiring any washing steps.•XOT3 was capable of effectively visualizing LDs in tissues and organs in mouse models of NAFLD. Aberrant alterations in the polarity of lipid droplets (LDs) are closely linked to disorders of lipid metabolism, which can result in LDs dysfunction and the onset of various diseases, including non-alcoholic fatty liver disease (NAFLD) and specific types of cancer. Therefore, it is imperative to comprehensively comprehend and accurately diagnose associated diseases by monitoring changes in LDs polarity in real time. In this paper, we designed and synthesized four novel fluorescent probes XOT1-XOT4 by using coumarin as a polarity-sensitive group and incorporate various triphenylamine derivatives as electron-donating groups, enabling specific targeting of LDs. All four probes possess high sensitivity towards minute polarity changes. Among them, XOT3 exhibited excellent photophysical properties and demonstrated a linear fluorescence change (R2 = 0.98596) within the polarity range of Δf = 0.023496 ∼ 0.047464. Moreover, probe XOT3 could be effectively utilized for visualizing intracellular LDs by precisely targeting them without requiring any washing steps. Importantly, probe XOT3 has been successfully utilized to monitor alterations in the polarity of LDs during apoptosis and ferroptosis as well as the quantity, size, and fluorescence intensity of LDs stimulated by oleic acid. Furthermore, probe XOT3 was capable of effectively visualizing LDs in tissues and organs in mouse models of non-alcoholic fatty liver disease (NAFLD), which provides a powerful tool for the early diagnosis of NAFLD. [Display omitted]