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(1Δg). 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(1Δg). 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(1Δg); 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(1Δg) 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(1Δg) have strong potential with respect to the enhancement of the efficacy of radiotherapy with exciting opportunities for cancer treatment.