Construction of Electroneutral Meso -Amide-BODIPY-Based AIE Fluorescent Probes for Lipid-Droplet Viscosity Imaging

Abstract Fluorescent molecular rotors for cellular viscosity have been widely developed to investigate the close relationships of viscosity with many associated diseases, among which the lipid-droplet (LD)-targeting and aggregation-induced emission (AIE)-type ones remain rarely reported. To realize these LD-targeting and AIE characters, herein, we first designed four electroneutral meso-amide BODIPY-based molecular rotors, explored viscosity/AIE properties, and cellular imaging for LD viscosity. Interestingly, by introducing the meso-amide-rigid phenyl group, BDP-Ph exhibited enhanced fluorescence at 526 nm in high viscous glycerol and AIE in water, while further introducing CF3, BDP-CF3Ph showed improved viscosity sensing properties and AIE in 80% water. In contrast, with the meso-amide-flexible groups (benzyl and n-butyl), BDP-Bn and BDP-Bu displayed moderate viscosity response performance and better AIE character even in pure water, which can be attributed to the presence of flexible groups avoiding the formation of large aggregates. Then, BDP-Ph and BDP-CF3Ph were chosen to evaluate the bioimaging for viscosity in living cells, which exhibited no toxicity and successfully responded to elevated intracellular viscosity through pretreatment with lipopolysaccharide and monensin. According to the similar structure with BODIPY 493/503, LD targeting subcellular localization experiments revealed that BDP-Ph and BDP-CF3Ph showed good Pearson’s correlation coefficients as high as 0.92 and 0.90, respectively. Fluorescence enhancements and numbers of LDs were clearly observed in oleic acid-induced lipid accumulation and autophagy models. Therefore, we for the first time reported and systematically investigate the meso-amide BODIPY-based electroneutral probes as AIE fluorescent rotors for cellular viscosity imaging in LDs.