A Glutathione Activatable Photosensitizer for Combined Photodynamic and Gas Therapy under Red Light Irradiation

Abstract

Although photodynamic therapy (PDT) is a promising approach for cancer therapy, most existing photosensitizers lack selectivity for tumor cells and the overexpressed glutathione (GSH) in tumor cells reduces the PDT efficiency. Therefore, designing photosensitizers that can be selectively activated within tumor cells and combine PDT with other therapeutic modalities represents a route for precise and efficient anticancer treatment. Herein, an organic activatable photosensitizer, CyI-DNBS, bearing 2,4-dinitrobenzenesulfonate (DNBS) as the cage group is reported. CyI-DNBS can be uptaken by cancer cells after which the cage group is selectively removed by the intracellular GSH, resulting in the generation of SO₂ for gas therapy. The reaction also releases the activated photosensitizer, CyI-OH, that can produce singlet oxygen (¹ O₂ ) under red light irradiation. Therefore, CyI-DNBS targets cancer cells for both photodynamic and SO₂ gas therapy treatments. The activatable photosensitizer provides a new approach for PDT and SO₂ gas synergistic therapy and demonstrates excellent anticancer effect in vivo.

Keywords: activatable photosensitizer; gas therapy; mitochondria-targeting; photodynamic therapy; red-light therapy.