Membrane-Targetable Dual-Responsive Fluorescent Probe for Simultaneous Detection of Polarity and Hypochlorite and Its Application in Apoptosis and Cancer Models

Cell plasma membrane (PM) polarity and near-membrane hypochlorous acid (HClO) play crucial roles in cellular communication, signal transduction, and redox homeostasis. Their dysregulation is closely linked to many physiological and pathological processes. However, due to the lack of suitable probes, simultaneous detection of both PM polarity and near-membrane HClO has remained unachievable. To address this challenge, we developed the first PM-targetable dual-responsive fluorescence probe (<b>DCVP-BF</b>_<b>2</b>) for detecting these parameters via distinct emission channels. The probe exhibits a red (λ_em = 638 nm) fluorescence enhancement upon decreasing polarity and a green (λ_em = 506 nm) fluorescence "turn-on" response to HClO with high sensitivity and selectivity. <b>DCVP-BF</b>_<b>2</b> features excellent photostability, low cytotoxicity, and an outstanding membrane-targeting ability. Using this probe, we revealed for the first time that there are concurrent increases in PM polarity and near-membrane HClO levels during cisplatin-induced apoptosis. Moreover, <b>DCVP-BF</b>_<b>2</b> enabled discrimination between cancer and normal cells via simultaneous dual-analyte imaging and achieved clear visualization of tumor tissues in mouse models. Compared with single-analyte detection methods, this dual-detection probe offers a more accurate and reliable approach for investigating membrane polarity and HClO-associated apoptosis and tumor imaging, holding considerable potential for exploring the membrane-related pathophysiological processes that involve polarity and HClO alterations.