Sulfone-Embedded NIR Fluorophore with Large Stokes Shift for Monitoring Viscosity Changes during NAFLD-Induced Ferroptosis

The accumulation of lipids in hepatocytes in nonalcoholic fatty liver disease (NAFLD) leads to an increase in reactive oxygen species and changes in the intracellular microenvironment, while ferroptosis is the result of the accumulation of iron-dependent lipid peroxidation. Studies have shown that ferroptosis plays an important role in the pathogenesis of NAFLD. Herein, we have developed a viscosity-sensitive fluorescence probe PTSO with near-infrared emission and a large Stokes shift, which were achieved by introducing the sulfone group into the dioxothiochromen-malononitrile fluorophore as an electron-withdrawing group. This probe showed satisfactory selectivity and sensitivity toward viscosity. Importantly, probe PTSO could discriminate between normal and tumor cells, and was further employed in monitoring the viscosity changes during NAFLD-induced ferroptosis. With the help of probe PTSO, our results have validated the close relationship between viscosity and ferroptosis in NAFLD at both cellular and tissue levels, potentially offering novel insights for the clinical diagnosis and treatment of NAFLD.