Targeted conversion from mitochondria to lipid droplets of nitrostyrylindolium by inserting only a styryl group

As highly dynamic cellular organelles responsible for the storage of neutral lipids, lipid droplets (LDs) assume crucial roles in maintaining lipid and energy metabolism. Hence, developing fluorescent probes for imaging the dynamics of LDs (generation, fusion, growth, and degradation) can offer valuable insights into numerous pathophysiological processes. This study highlights a targeted conversion strategy for promptly fabricating a novel LD fluorescent probe named NSSI by simply inserting a styryl group into nitrostyrylindolium (IR-418), a well-known mitochondria-targeted probe. The insertion of a styryl group enables an increase in the lipophilicity of NSSI (ClogP = 6.37) compared with the parent IR-418 (ClogP = 4.10), thereby facilitating its embedding into the waterless core of LDs via hydrophobic interaction, along with an interface-targeting through the electrostatic interaction between its indolium moiety and the negatively charged polar shell of LDs, to achieve its specific targeting towards LDs. By utilizing NSSI, we have successfully monitored the morphology and dynamic alterations of LDs in diverse cellular models. We have also observed the LD distribution differences between the infarcted and normal regions in the brain tissues of a photothrombosis stroke mouse model, visualized disrupted hepatic cords and severe steatosis within the liver tissues of an acute liver failure (ALF) mouse model, and witnessed the lipid-rich areas in zebrafish embryos. Overall, these findings signify the potential of NSSI as a highly versatile tool for dynamic LD imaging, whether in cellular models, tissue samples, or in vivo scenarios.