ESIPT-based Fluorescent Dyes For Dynamic Lipid Droplet

Lipid droplets(LDs)have been taken as simple and inert fat particles in cells that store neutral lipids for a long time.However,with further research,people has gradually realized that LDs play an important role in maintaining intracellular homeostasis cell as complex and dynamic organelles.Lipid abnormalities can also induce various diseases,for instance,obesity,fatty liver,type 2 diabetes,atheroma and even cancer.Therefore,it is of great significance to study physiological and pathological functions of LDs and develop tools used for monitoring the dynamic changes of intracellular LDs.Fluorescence imaging as an important labeling method can be used to reveal physiological activities in living organisms and study changes and functions of intracellular LDs.Based on these,scientists have developed a variety of LDs fluorescent dyes.However,most of them have a number of limitations,for example,poor specificity of LDs targeting,strong interference of background fluorescence,low signal-to-noise ratio and difficulty in synthesis.ESIPT-based 3-Hydroxyflavone(3HF)derivatives as typical fluorescent molecules,have many advantages compared with other fluorescent dyes,for instance,larger Stokes shift and better sensitivity to solvent polarity.And they have been widely used in the detection of microenvironment changes.In this paper,3HF was used as the parent to develop a series of fluorescent dyes(Flps)for detecting the dynamic changes of lipid droplets in cells and tissues.Firstly,we screened the 4’-position substituent of 3HF and found that 4’-dialkylamino-substituted 3HF can image intracellular LDs.Flps exhibited the best intracellular LDs targeting when the carbon chain length of 4’-dialkylamino was in 2-4 range(Flp-(11-13))and no heterocyclic atoms were introduced into substituent.The fluorescence of dyes spanned from yellow to red through modifying more conjugated group(Flp-19)in the structure of Flp-11 under the premise of ensuring LDs targeting of dyes.Additionally,Flps showed lower cytotoxicity,lower dyes using concentration and more quickly dying than BODIPY 493/503,a traditional LDs fluorescent dye.And Flps successfully served for monitoring the dynamic nature and accumulation of LDs in living cells.Subsequently,Flps were used for high-fidelity imaging of LDs in 4 mouse tissue.Therefore,we believe Flps could be widely used in further LDs studies and medical diagnosis.