Donor Optimizing to Boost Type I and Type II Photosensitization for Solid Tumor Therapy

Organic photosensitizer DE with strong Type I&II photosensitization is realized through the donor optimizing method, which generates 9 times more ¹O₂ than Type II PS Ce6 under normoxia conditions and 2.9 fold more •OH than Type I PS RB. DE has proven to be an efficient PS for solid tumor therapy, offering a promising paradigm for developing PSs for PDT.

Abstract

Oxygen-less dependent Type I photosensitizers (PSs) have emerged as a crucial strategy for enhancing photodynamic therapy efficiency in treating hypoxic tumors. However, solid tumors have normoxia regions situated near functional blood vessels and hypoxia regions in their interiors. To maximize the utilization of oxygen within solid tumors, herein a viable donor optimizing approach is developed to enhance both Type I&II reactive oxygen species generation of PSs. At the same mole concentration, one optimized PS (named DE) generated 9 times more ¹O₂ than commercial Type II PS Chlorin e6 upon white light irradiation for 60 s. Compared to the commercial Type I PS Rose Bengal, •OH generation by DE is 2.9 times more under the hypoxia condition. With its optimized Type I&II pathway under normoxia and hypoxia conditions, DE is proven to be an efficient PS for solid tumor treatment, offering a promising approach for PS development.