Engineering of a NIR fluorescent probe for high-fidelity tracking of lipid droplets in living cells and nonalcoholic fatty liver tissues

LDs (Lipid droplets) are key organelles for lipid metabolism and storage, which are closely related to ferroptosis and fatty liver. Due to its small size and highly dynamic nature, developing high-fidelity fluorescent probes for imaging of LDs is crucial for observing the dynamic physiological processes of LDs and investigating LDs-associated diseases. Herein, we synthesized three dicyanoisophorone-based fluorescent probes (DCIMe, DCIJ, and DCIQ) with different electron-donating groups and studied their imaging performance for LDs. The results show that DCIQ is highly polarity sensitive and can perform high-fidelity imaging for LDs, with significantly better performance than DCIMe, DCIJ, and commercial LD probe BODIPY 493/503. Based on this, DCIQ was successfully applied to real-time observe the interplays between LDs and other organelles (mitochondria, lysosomes, and endoplasmic reticulum), and to image the dynamics of LDs with fast scanning mode (0.44 s/frame) and the generation of oleic acid-induced LDs with high-fidelity. Finally, DCIQ was used to study the changes of LDs in the ferroptosis process and nonalcoholic fatty liver disease tissues. Overall, this study provided a powerful tool for high-fidelity imaging of LDs in cells and tissues.