A GSH-activated dual-channel fluorescent probe for cancer cell theranostics and in vivo zebrafish imaging

The elevated glutathione (GSH) levels in cancer cells present a key opportunity for integrated therapeutic-diagnostic strategies. Leveraging this characteristic, we develop a GSH-activated theranostic probe, Np-DOX, which links a sulfonamide-containing naphthalimide derivative with the anti-tumor drug doxorubicin (DOX). Notably, under excitation at 390 nm and 480 nm, the fluorescence of the naphthalimide moiety and the intrinsic red emission of DOX enable dual-channel real-time imaging of drug release, respectively. Moreover, Np-DOX can effectively distinguish tumor cells from normal cells through marked changes in fluorescence intensity in the dual-emission channels. Furthermore, GSH-triggered activation of Np-DOX allows for the concurrent release of sulfur dioxide (SO₂) and DOX, resulting in a synergistic antitumor effect through the combination of SO₂ gas therapy and chemotherapy. Therefore, Np-DOX represents a promising theranostic platform for monitoring drug delivery while exerting potent anticancer activity.