Simultaneously Achieving Lipid-Droplet-Location and Activity-Based Fluorogenic Sensing of Hydrogen Peroxide by Dicyanofuran-Fused Coumarin Derivatives

Activity-based sensing of hydrogen peroxide (H2O2) in specific organelles of interest is significant for deciphering its physiological functions at the subcellular level. However, currently reported H2O2-responsive moieties lack organelle targetability, necessitating an auxiliary navigation to direct the probe molecule to the targeted cellular local region. Herein, we propose an economical strategy by integrating a dual-functional moiety that combines molecular recognition and organelle targeting. By exploiting the oxidation reaction of dicyanofuran, two novel H2O2-activatable probes capable of targeting lipid droplets (LDs) were rationally designed based on the coumarin scaffold. Notably, the dicyanofuran-fused coumarin derivative FC1 could effectively image endogenous and exogenous H2O2 in LDs of living cells and has been successfully utilized to distinguish cancer cells from normal cells by leveraging the synergistic combination of elevated H2O2 levels and LD abundance. Our work not only presents a new activity-based sensing mechanism for H2O2 but also provides a versatile approach for the development of subcellular fluorescent probes in the future.