Near-Infrared Fluorescent Lipid Droplet Polarity Probe for Distinguishing Different Liver Injury Diseases

Lipid droplets (LDs), pivotal subcellular organelles, undergo substantial changes in number, size, distribution, and polarity during liver disease progression. These alterations not only reflect disease advancement but also serve as potential targets for diagnosis and therapy. Developing methods to visualize LDs and monitor their dynamic changes is therefore of crucial scientific significance for elucidating the link between LDs and liver injury. Here, we designed and synthesized three LD-targeted, polarity-sensitive fluorescent probes (TXD-1, TXD-2, TXD-3) for liver disease research. TXD-3 stood out with optimal performance, featuring near-infrared (NIR) emission at 760 nm, a large Stokes shift (138 nm), low cytotoxicity, excellent LD-targeting, and sensitive polarity response. Cell imaging studies show that TXD-3 can distinguish the lipid metabolism differences between tumor cells and normal cells. In addition, TXD-3 can precisely monitor the variations of LDs during sorafenib treatment and effectively distinguish between steatosis and phospholipidosis, providing key information support for drug development. In vivo, TXD-3 can sensitively detect hepatic LD abnormalities in acute alcoholic liver injury (AALI) and nonalcoholic fatty liver disease (NAFLD), and unravel the mechanism differences between these diseases, providing a valuable molecular probe tool for advancing the pathological mechanism research of liver diseases.