Sulfone-Embedded\nNIR Fluorophore with Large Stokes\nShift for Monitoring Viscosity Changes during NAFLD-Induced Ferroptosis

The accumulation of lipids in hepatocytes\nin nonalcoholic\nfatty\nliver disease (NAFLD) leads to an increase in reactive oxygen species\nand changes in the intracellular microenvironment, while ferroptosis\nis the result of the accumulation of iron-dependent lipid peroxidation.\nStudies have shown that ferroptosis plays an important role in the\npathogenesis of NAFLD. Herein, we have developed a viscosity-sensitive\nfluorescence probe PTSO with near-infrared emission and a large Stokes\nshift, which were achieved by introducing the sulfone group into the\ndioxothiochromen-malononitrile fluorophore as an electron-withdrawing\ngroup. This probe showed satisfactory selectivity and sensitivity\ntoward viscosity. Importantly, probe PTSO could discriminate between\nnormal and tumor cells, and was further employed in monitoring the\nviscosity changes during NAFLD-induced ferroptosis. With the help\nof probe PTSO, our results have validated the close relationship between\nviscosity and ferroptosis in NAFLD at both cellular and tissue levels,\npotentially offering novel insights for the clinical diagnosis and\ntreatment of NAFLD.