A Bright Two‐Photon Lipid Droplets Probe with Viscosity‐Enhanced Solvatochromic Emission for Visualizing Lipid Metabolic Disorders in Deep Tissues

Abstract The polarity of lipid droplets (LDs) plays an important role in pathological processes associated with abnormal lipid metabolism. Monitoring the variation of LDs polarity in cells and tissues is of great importance in biomedical research and clinical diagnosis. However, developing fluorescent LDs‐specific probes with high polarity sensitivity, brightness, and permeability for deep tissue imaging is still challenging. Herein, a push–pull fluorescent luminogen (DPBT) with aggregation‐induced emission, strong solvatochromism, large Stokes shift, high solid‐state fluorescence efficiency and superior two‐photon absorption is facilely developed. The lipophilic DPBT can specifically stain LDs with high biocompatibility and good photostability. The viscosity‐enhanced solvatochromic emission property enables DPBT to visualize LDs polarity with high brightness and imaging contrast, and deep penetration depth under two‐photon microscopy. DPBT can specifically stain lipids in various mouse tissues (atherosclerotic plaque, liver, and mesenteric adipose tissues) and map their polarity distribution to reflect lipid metabolic states within those tissues. It is found that the lipids deposition as well as their polarity distribution in tissues of hyperlipoidemia mouse are clearly different from the tissues of the normal mouse. Its excellent properties make DPBT a promising candidate for investigating LDs‐associated physiological and pathological processes in live biological samples.