Charge‐Regulation Activable Theranostic Probe for Tumor‐Specific Fluorescence Imaging and Chemo‐Phototherapy

Activable theranostic probes offer significant potential for the precise diagnosis and therapy in cancer treatment. The core challenge in realizing this target is how to manipulate therapeutic and imaging activities by a simple yet efficient method. To address this, an exceptional "charge regulation" strategy to furnish an activable theranostic probe, GSH-Cy5 is employed. The probe undergoes tumor-specific activation via glutathione (GSH)-triggered decationization, concurrently enhancing its anti-cancer activity and tumor-imaging contrast. Beyond this theranostic activity, GSH-Cy5 also exhibits synergistic photothermal (PTT) and photodynamic (PDT) effects, which further amplify its therapeutic efficacy by inducing cell death through mitochondria-mediated pathways. In vivo experiments demonstrated the effectiveness of GSH-Cy5, as it successfully enabled tumor visualization and selective therapy in tumor-bearing mouse models. This work establishes GSH-Cy5 as a transformative theranostic platform, while the "charge regulation" strategy opens new avenues for designing activable cyanine probes in precise tumor treatment.