Harnessing polarity-dependent fluorescent probe for lipid droplet metabolism dissection and in vivo nonalcoholic fatty liver disease diagnosis

Nonalcoholic fatty liver disease (NAFLD) has emerged as a prevalent chronic liver condition worldwide. The dysregulated metabolism of lipid droplets (LDs) in cells is physiologically and pathologically linked to NAFLD. The development of fluorescent probes for imaging LD metabolism holds promise for noninvasive diagnosis and understanding of NAFLD. However, the development of such probes is challenging, and their in vivo diagnostic potential remains largely unexplored. Here, we present the synthesis of ZP-1, a bright fluorophore serving as a specific probe for LDs. ZP-1 possesses a donor-acceptor electronic structure with intramolecular charge transfer characteristics and shows polarity-dependent emission. In highly polar solvents, such as water, ZP-1 exhibits minimal fluorescence, while in low-polarity solvents, it displays strong fluorescence. This property enables high-specificity LD detection with excellent imaging contrast. Attributed to its high photostability and pH stability, ZP-1 effectively visualizes LD metabolism in live cells via real-time imaging, encompassing processes such as growth, migration, fusion, and fission. Moreover, we demonstrate in vivo diagnosis of NAFLD in a mouse model, providing rich information regarding LD morphology, numbers, volumes, and tissue structures. This work introduces ZP-1 as a valuable tool for NAFLD diagnosis and research, facilitating noninvasive assessment and improved understanding of the disease.