A Dual-Responsive Ratiometric Fluorescent Probe for Simultaneous Monitoring of Lipophagy and HOCl in Non-alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disorder closely associated with dysregulated lipid metabolism and increased oxidative stress. To better understand the underlying pathological mechanisms of NAFLD and identify potential therapeutic strategies, we developed a novel dual-response fluorescent probe, Pola-HOCl, which enables the simultaneous monitoring of intracellular lipid droplet polarity and hypochlorous acid (HOCl) levels, providing new perspectives for the potential early diagnosis and treatment of NAFLD. By employing the through bond energy transfer (TBET) mechanism, Pola-HOCl minimizes spectral crosstalk, ensuring precise and reliable measurements. Both in vitro and in vivo experiments demonstrated that Pola-HOCl exhibits superior sensitivity and specificity in detecting lipid droplet dynamics and oxidative stress, offering valuable insights into the role of lipophagy in mitigating oxidative damage in NAFLD. This study underscores the practical application of Pola-HOCl for investigating the complex interplay between lipophagy and oxidative stress, and introduces a novel approach to explore the pathophysiological mechanisms underlying NAFLD.