A lipid droplet-targeted fluorescent probe for fluorescence imaging of cell and zebrafish viscosity†

Lipid droplets (LDs) represent highly dynamic organelles found in almost all organisms and play a pivotal role in regulating the balance of intracellular lipid homeostasis. Viscosity directly affects the metabolism of lipid droplets, and the abnormal change of viscosity will lead to a series of related diseases. Therefore, developing a tool that can monitor changes in intracellular lipid droplet viscosity in real-time is of great significance for disease prevention, diagnosis, and treatment. In this study, a viscosity-sensitive fluorescent probe CA-LD based on an intramolecular twisted charge transfer (TICT) mechanism was developed. The CA-LD probe exhibited strong fluorescence emission at approximately 640 nm and showed a 161-fold increase in fluorescence intensity in 99% glycerol compared to water. Additionally, the probe CA-LD demonstrated the advantages of good anti-interference, excellent biocompatibility and good photostability. Significantly, because of the probe's sensitivity to viscosity, the probe CA-LD successfully distinguished normal cells from cancer cells and has been able to visualize changes in lipid droplets’ viscosity induced by oleic acid. In addition, the probe CA-LD was effectively employed to monitor changes in the viscosity of cells and zebrafish induced by different drugs. Therefore, the probe CA-LD can provide an effective means for the detection of lipid droplet viscosity changes and is of great value for physiological diagnosis, pathological analysis and medical research on related diseases.