A comparison of the radiosensitisation ability of 22 different element metal oxide nanoparticles using clinical megavoltage X-rays

Background A wide range of nanoparticles (NPs), composed of different elements and their compounds, are being developed by several groups as possible radiosensitisers, with some already in clinical trials. However, no systematic experimental survey of the clinical X-ray radiosensitising potential of different element nanoparticles has been made. Here, we directly compare the irradiation-induced (10 Gy of 6-MV X-ray photon) production of hydroxyl radicals, superoxide anion radicals and singlet oxygen in aqueous solutions of the following metal oxide nanoparticles: Al 2 O 3 , SiO 2 , Sc 2 O 3 , TiO 2 , V 2 O 5 , Cr 2 O 3 , MnO 2 , Fe 3 O 4 , CoO, NiO, CuO, ZnO, ZrO 2 , MoO 3 , Nd 2 O 3 , Sm 2 O 3 , Eu 2 O 3 , Gd 2 O 3 , Tb 4 O 7 , Dy 2 O 3 , Er 2 O 3 and HfO 2 . We also examine DNA damage due to these NPs in unirradiated and irradiated conditions. Results Without any X-rays, several NPs produced more radicals than water alone. Thus, V 2 O 5 NPs produced around 5-times more hydroxyl radicals and superoxide radicals. MnO 2 NPs produced around 10-times more superoxide anions and Tb 4 O 7 produced around 3-times more singlet oxygen. Lanthanides produce fewer hydroxyl radicals than water. Following irradiation, V 2 O 5 NPs produced nearly 10-times more hydroxyl radicals than water. Changes in radical concentrations were determined by subtracting unirradiated values from irradiated values. These were then compared with irradiation-induced changes in water only. Irradiation-specific increases in hydroxyl radical were seen with most NPs, but these were only significantly above the values of water for V 2 O 5 , while the Lanthanides showed irradiation-specific decreases in hydroxyl radical, compared to water. Only TiO 2 showed a trend of irradiation-specific increase in superoxides, while V 2 O 5 , MnO 2 , CoO, CuO, MoO 3 and Tb 4 O 7 all demonstrated significant irradiation-specific decreases in superoxide, compared to water. No irradiation-specific increases in singlet oxygen were seen, but V 2 O 5 , NiO, CuO, MoO 3 and the lanthanides demonstrated irradiation-specific decreases in singlet oxygen, compared to water. MoO 3 and CuO produced DNA damage in the absence of radiation, while the highest irradiation-specific DNA damage was observed with CuO. In contrast, MnO 2 , Fe 3 O 4 and CoO were slightly protective against irradiation-induced DNA damage. Conclusions Beyond identifying promising metal oxide NP radiosensitisers and radioprotectors, our broad comparisons reveal unexpected differences that suggest the surface chemistry of NP radiosensitisers is an important criterion for their success.