Fluorescent probe for simultaneous visualization of lipid peroxidation and lipid droplets accumulation in living cells.

BACK GROUND: Lipid peroxidation (LPO) and abnormal accumulation of lipid droplets (LDs) are key pathogenic factors contributing to the onset and progression of multiple diseases. Fluorescent probes for monitoring LPO and LDs accumulation are promising tools for the early diagnosis of related diseases, providing valuable insights that could lead to improved disease management and therapeutic strategies. However, to the best of our knowledge, a dual-channel fluorescent probe capable of simultaneously monitoring LPO and LD accumulation has not yet been reported.

RESULTS: We rationally designed and synthesized a dual-responsive fluorescent probe, Cou-LPO4, for simultaneous visualization of LPO and LDs in living cells. Cou-LPO4 exhibits green fluorescence at 560 nm in response to lipid peroxyl radicals (LOO•) with excellent selectivity and sensitivity, and red fluorescence at 640 nm in response to LDs accumulation. Cou-LPO4 was successfully applied to evaluate LPO during RSL3-and erastin-induced ferroptosis by monitoring fluctuations in LOO• levels. Subsequently, using Cou-LPO4, we revealed a significant upregulation of LPO, accompanied by a marked accumulation of LDs in nonalcoholic fatty liver disease (NAFLD) cell model.

SIGNIFICANCE: Cou-LPO4 is the first dual-channel fluorescent probe enabling simultaneous monitoring of LPO and LDs accumulation in living cells. It provides a powerful tool for studying LPO and LDs accumulation-related diseases like NAFLD, offering new insights for early diagnosis and therapeutic strategies.