A multifunctional fluorescent probe towards lipid droplets polarity and SO2 for visualization of cancer, inflammation, ferroptosis, and acute alcoholic liver injury in vivo

Background Sulfur dioxide (SO 2 ) and lipid droplets (LDs) polarity are critical regulators in various physiological and pathological processes, and the related research has been hampered by the lack of integrated detection tools in biological samples and multi disease models. Results Herein, we presented a dual-responsive fluorescent probe TDTB to concurrently monitor SO 2 and LDs polarity. Based on the D-π-A architecture, TDTB was constructed by integrating hydrophobic triphenylamine (TPA) group for LDs-specific sensing (λ em  = 670 nm) with Michael receptor as SO 2 recognition group (λ em  = 489 nm). We demonstrated TDTB had typical AIE characteristics and polar-sensitivity, and could specifically target LDs (Pearson's coefficient r = 0.88). Meanwhile, TDTB exhibited remarkable fluorescence enhancement (about 765-fold) with increased SO 2 , as well as excellent selectivity and anti-interference properties in both physiological buffers and cells. Further, with TDTB , we also realized real-time tracking of endogenous SO 2 fluctuations and LDs polarity alteration across cellular, tissues, and in vivo models. Notably, TDTB was successfully applied in pioneering visualization of acute alcoholic liver injury (AALI), diagnosing cancer, inflammation, and ferroptosis. Significance Our research not only provided a versatile tool for decoding SO 2 -LDs polarity crosstalk but also advanced the understanding of their roles in multi-disease pathogenesis, offering new avenues for mechanistic and therapeutic exploration.