X-ray induced singlet oxygen generation by nanoparticle-photosensitizer conjugates for photodynamic therapy: determination of singlet oxygen quantum yield

Abstract

Singlet oxygen is a primary cytotoxic agent in photodynamic therapy. We show that CeF ₃ nanoparticles, pure as well as conjugated through electrostatic interaction with the photosensitizer verteporfin, are able to generate singlet oxygen as a result of UV light and 8 keV X-ray irradiation. The X-ray stimulated singlet oxygen quantum yield was determined to be 0.79 ± 0.05 for the conjugate with 31 verteporfin molecules per CeF ₃ nanoparticle, the highest conjugation level used. From this result we estimate the singlet oxygen dose generated from CeF ₃-verteporfin conjugates for a therapeutic dose of 60 Gy of ionizing radiation at energies of 6 MeV and 30 keV to be (1.2 ± 0.7) × 10 ⁸ and (2.0 ± 0.1) × 10 ⁹ singlet oxygen molecules per cell, respectively. These are comparable with cytotoxic doses of 5 × 10 ⁷–2 × 10 ⁹ singlet oxygen molecules per cell reported in the literature for photodynamic therapy using light activation. We confirmed that the CeF3-VP conjugates enhanced cell killing with 6 MeV radiation. This work confirms the feasibility of using X- or γ- ray activated nanoparticle-photosensitizer conjugates, either to supplement the radiation treatment of cancer, or as an independent treatment modality.