Chen Yanli, Li Wenqing, Li Shuai, Liu Li, Yang Jing, Wang Peng
Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China.
ACS Sens. 2025 Jan 24;10(1):398-406. doi: 10.1021/acssensors.4c02699. Epub 2024 Dec 30.
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.
非酒精性脂肪性肝病（NAFLD）中肝细胞内脂质的积累会导致活性氧的增加和细胞内微环境的变化，而铁死亡是铁依赖性脂质过氧化积累的结果。研究表明，铁死亡在NAFLD的发病机制中起重要作用。在此，我们开发了一种具有近红外发射和大斯托克斯位移的粘度敏感荧光探针PTSO，这是通过将砜基作为吸电子基团引入二氧代硫代色烯-丙二腈荧光团实现的。该探针对粘度表现出令人满意的选择性和灵敏度。重要的是，探针PTSO可以区分正常细胞和肿瘤细胞，并进一步用于监测NAFLD诱导的铁死亡过程中的粘度变化。借助探针PTSO，我们的结果在细胞和组织水平上验证了NAFLD中粘度与铁死亡之间的密切关系，可能为NAFLD的临床诊断和治疗提供新的见解。
