Octahedral molybdenum clusters as radiosensitizers for X-ray induced photodynamic therapy

Abstract

The use of radiosensitizers recently emerged as a promising approach to circumvent the depth penetration limitations of photodynamic therapy of cancer and to enhance radiotherapeutical effects. A widely explored current strategy is based on complex nanoarchitectures that facilitate the transfer of energy harvested from X-ray radiation by scintillating nanoparticles to the surrounding photosensitizer molecules to generate reactive oxygen species, mostly singlet oxygen O₂(¹Δ_g). We describe an alternative approach aiming at a considerable simplification of the architecture. The presented nanoparticles, made of the luminescent octahedral molybdenum cluster compound (n-Bu₄N)₂[Mo₆I₈(OCOCF₃)₆], efficiently absorb X-rays due to the high content of heavy elements, leading to the formation of the excited triplet states that interact with molecular oxygen to produce O₂(¹Δ_g). The activity of the nanoparticles on HeLa cells was first investigated under UVA/blue-light irradiation in order to prove the biological effects of photosensitized O₂(¹Δ_g); there is no dark toxicity at micromolar concentrations, but strong phototoxicity in the nanomolar range. The nanoparticles significantly enhance the antiproliferative effect of X-ray radiation in vitro at lower concentration than for previously reported O₂(¹Δ_g) radiosensitizing systems and this effect is more pronounced on cancer HeLa cells than non-cancer MRC cells. The results demonstrate that the cluster-based radiosensitizers of O₂(¹Δ_g) have strong potential with respect to the enhancement of the efficacy of radiotherapy with exciting opportunities for cancer treatment.