Dual-Targeting Ratiometric Fluorescent Probe for Visualizing Changes in HClO and Polarity in Lipid Droplets and Mitochondria

Cuproptosis is a mode of cell death caused by the accumulation of copper ions and involves mitochondrial dysfunction. Changes in the hypochlorous acid (HClO) content and polarity in cells are closely associated with many diseases and are inevitable parts of physiological processes. At the subcellular level, no method has yet been developed for simultaneously detecting HClO and polarity changes in both mitochondria and lipid droplets. To fill this gap, in this study, we successfully constructed a dual-targeted ratiometric fluorescent probe (N-Pol-HClO). This probe was developed by using functional polysiloxanes as a fluorescent platform. It is capable of simultaneously detecting HClO and polarity changes in lipid droplets and mitochondria. The probe has excellent biocompatibility and photostability and can dynamically track HClO and polarity changes in live cells and zebrafish. In addition, this study allows for the real-time monitoring of HClO in lipid droplets and mitochondria during cuproptosis. We hope that this study will open new avenues for the development of novel fluorescent probes and provide powerful technical support for physiological and pathological studies.