Quasi-intrinsic thiobase derivatives as potential targeted photosensitizers in two-photon photodynamic therapy

Abstract

In this study, a set of potential quasi-intrinsic photosensitizers for two-photon photodynamic therapy (PDT) are proposed based on the unnatural 2-amino-8-(1′-β-ᴅ-2′-deoxyribofuranosyl)-imidazo[1,2-ɑ]-1,3,5-triazin-4(8H)-one (P), which is paired with the 6-amino-5-nitro-3-(1′-β-ᴅ-2′-deoxyribofuranosyl)-2(1H)-pyridone (Z) and can specifically recognize breast and liver cancer cells. Herein, the effects of sulfur substitution and electron-donating/electron-withdrawing groups on the photophysical properties in aqueous solution are systematically investigated. The one- and two-photon absorption spectra evidence that the modifications could result in red-shifted absorption wavelength and large two-photon absorption cross-section, which contributes to selective excitation and provides effective PDT for deep-seated tissues. To ensure the efficient triplet state population, the singlet–triplet energy gaps and spin–orbit coupling constants were examined, which is responsible for a rapid intersystem crossing rate. Furthermore, these thiobase derivatives are characterized by the long-lived T1 state and the large energy gap for radiationless transition to ensure the generation of cytotoxic singlet oxygen.