Fluorescent probes with dual-targeting organelles monitor polarity in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) becomes a world health issue due to its rising prevalence and lack of a definitive pathogeny. However, the excessive accumulation of fat droplets has been recognized as a crucial characteristic of NAFLD, accompanied with endoplasmic reticulum stress in its onset and progression as well. Therefore, real-time monitoring the dynamic of lipid droplets (LDs) and endoplasmic reticulum (ER) within cells is paramount. In this regard, four D-A-π-D structural fluorescent probes COB1-COB4 were designed and synthesized wherein coumarin connected with carbazole acted as precursors while the side chains attached to carbazole groups are different. Here, probes COB1-COB4 exhibited high sensitivity towards polarity, while COB2 was chosen for further study attributing to its excellent anti-interference property. Cell imaging demonstrated that COB2 could accurately target both LDs and ER at the same time and monitor the changes of the two organelles under different physiological conditions. Notably, probe COB2 also exhibited the ability to distinguish normal liver from fatty liver at the tissue level. The above results lay an experimental foundation for developing novel dual-targeted probes with potential for early diagnosis of non-alcoholic fatty liver.