Development of a water-soluble polarity/reactive nitrogen species dual-responsive fluorescence probe with enhanced specificity/sensitivity for early-stage non-alcoholic fatty liver disease diagnosis.

Non-alcoholic fatty liver disease (NAFLD) is a global health concern, but early diagnosis remains challenging due to the limitations of current methods, which are often invasive or lack sensitivity. To address this, we developed UIO-YB, a dual-responsive fluorescence probe combining water-soluble UIO carriers with a polarity-sensitive dye (YB) for precise NAFLD detection. UIO-YB exhibits dual fluorescence emission (red for YB, blue for UIO), enabling simultaneous detection of lipid accumulation (via YB's polarity response) and oxidative stress markers (via UIO's RNS reactivity). In vitro, UIO-YB detected lipid droplets in HepG2 cells within 2 h, surpassing Oil Red O in speed and simplicity. In vivo, it accurately visualized Hepatic steatosis in mice after 6 weeks of a high-fat diet, demonstrating high specificity and sensitivity. Unlike conventional dyes, UIO-YB operates without organic solvents, simplifying protocols while reducing background noise. UIO-YB's water solubility and dual-response design overcome key limitations of existing probes, offering a rapid, scalable tool for early NAFLD detection. Its performance in cellular and preclinical models highlights its potential to advance NAFLD research and clinical diagnostics. This innovation paves the way for non-invasive, high-sensitivity imaging to improve disease monitoring and intervention.