A lipid droplet‐selective fluorescent probe for real‐time imaging and polarity sensing

Abstract Lipid droplets (LDs) are dynamic organelles involved in lipid storage and metabolism, interacting with other organelles to maintain cellular homeostasis. Changes in LD number, size, or polarity are linked to metabolic disorders such as fatty liver disease, diabetes, and drug‐induced liver injury. Fluorescence imaging is a sensitive, non‐invasive method for monitoring LD dynamics in living systems. However, many existing LD‐targeting dyes lack the specificity and functionality required to track real‐time changes in the lipid microenvironment. Recent advances in environment‐sensitive fluorophores, particularly those using excited‐state intramolecular proton transfer, offer promising tools for visualizing LD behavior and detecting early hepatic steatosis. In this study, probe 1 demonstrated high lipid selectivity, excellent biocompatibility, and pronounced polarity sensitivity, enabling real‐time visualization of LD dynamics and early‐stage hepatic steatosis detection in living cells. Its photophysical behavior and selectivity were analyzed using density functional theory (DFT), time‐dependent DFT, and confocal laser scanning microscopy.