A Singlet Photosensitizer for Superoxide Radical Mediated Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) hinges on three pivotal components: light, triplet photosensitizers and molecular oxygen. Yet, the modulation of triplet states within photosensitizers is inherently challenging, constrained by the spin selection rules that limit universal regulation through chemical modification. Moreover, the pervasive hypoxic conditions within tumor tissues critically impede singlet oxygen generation. To transcend these barriers, we developed a singlet state-based photosensitization strategy with the production of superoxide anion radicals. Briefly, pyridinium as an acceptor was used to capture the excited state electron of the dye to form a charge-separated state radical, remarkably prolonging the lifetime of the excited states to ensure electron transfer from charge-separated state radical to molecular oxygen. The photosensitization mechanism predicated on the singlet excited state of the photosensitizer and circumvented the stringent reliance on molecular oxygen, similar to the traditional Type-I photosensitizers, within the tumor microenvironment. We denominated it as the Type-0 photosensitizer. Through comprehensive theoretical and experimental validation, we substantiated the viability of this photosensitization process and its feasibility for cancer PDT in vivo.