HClO-Activatable Organelle-Targeted Theranostic Probes for Real-Time Imaging and On-Demand Elimination of H1N1-Infected Cells

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Abstract Influenza A (H1N1) virus infection disrupts intracellular homeostasis, inducing endoplasmic reticulum (ER) stress, Golgi apparatus stress, and elevated hypochlorous acid (HClO) production. Simultaneously visualizing these events and intervening in a timely manner is crucial for both infection progression assessment and effective antiviral therapy. Herein, we report a tunable, organelle-targeting, HClO-activatable theranostic platform constructed by integrating a naphthalimide fluorophore with methylene blue (MB) and functionalized with specific organelle-targeting moieties. This molecular design yields two intelligent probes, ER-HClO and Golgi-HClO, which selectively localize to the ER and Golgi, respectively. The platform operates through a modular mechanism: the naphthalimide unit provides stable green fluorescence, serving both as a localizer for organelle tracking and as an internal reference for ratiometric imaging of HClO, while leuco-MB remains inert until encountering elevated HClO, a hallmark of virus-infected cells, via HClO-triggered amide cleavage, which releases cationic MB+ that generates turn-on NIR fluorescence and restores photodynamic activity. Using this platform, we visualized progressive ER and Golgi morphological remodeling during H1N1 infection together with a temporal increase in HClO-responsive fluorescence signals. HClO-triggered photodynamic activation further enabled selective elimination of H1N1-infected cells under light irradiation. This work established a versatile theranostic platform integrating organelle-resolved structural imaging, oxidative-stress monitoring, and on-demand photodynamic intervention, providing a promising strategy for selective photodynamic intervention in H1N1-infected cells.

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