A glutathione-activated anthraquinone-based photosensitizer for selective photodynamic therapy of cancer cells overexpressing glutathione

An anthraquinone derivative 2 was found to induce protein degradation under neutral conditions and without additives upon visible light irradiation. Based on this finding, a glutathione (GSH)-activatable photosensitizer 3 was designed and synthesized. 3 showed minimal photoactivity in the absence of GSH, but upon reaction with GSH, it generated a highly active species that caused selective photo-cytotoxicity toward cancer cells with elevated intracellular GSH levels. These results demonstrate the potential of anthraquinone-based systems as tunable and tumor-selective photosensitizers for photodynamic therapy. • A simple anthraquinone derivative 2 was found to degrade proteins upon irradiation with visible light. • A novel glutathione (GSH)-activatable photosensitizer 3 was designed and synthesized based on 2 . • 3 showed negligible photosensitizing ability in the absence of GSH. • 3 exhibited photo-cytotoxicity against only cancer cells expressing high levels of GSH when irradiated with visible light.