Abstract
BackgroundA 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: Al2O3, SiO2, Sc2O3, TiO2, V2O5, Cr2O3, MnO2, Fe3O4, CoO, NiO, CuO, ZnO, ZrO2, MoO3, Nd2O3, Sm2O3, Eu2O3, Gd2O3, Tb4O7, Dy2O3, Er2O3 and HfO2. We also examine DNA damage due to these NPs in unirradiated and irradiated conditions.ResultsWithout any X-rays, several NPs produced more radicals than water alone. Thus, V2O5 NPs produced around 5-times more hydroxyl radicals and superoxide radicals. MnO2 NPs produced around 10-times more superoxide anions and Tb4O7 produced around 3-times more singlet oxygen. Lanthanides produce fewer hydroxyl radicals than water. Following irradiation, V2O5 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 V2O5, while the Lanthanides showed irradiation-specific decreases in hydroxyl radical, compared to water. Only TiO2 showed a trend of irradiation-specific increase in superoxides, while V2O5, MnO2, CoO, CuO, MoO3 and Tb4O7 all demonstrated significant irradiation-specific decreases in superoxide, compared to water. No irradiation-specific increases in singlet oxygen were seen, but V2O5, NiO, CuO, MoO3 and the lanthanides demonstrated irradiation-specific decreases in singlet oxygen, compared to water. MoO3 and CuO produced DNA damage in the absence of radiation, while the highest irradiation-specific DNA damage was observed with CuO. In contrast, MnO2, Fe3O4 and CoO were slightly protective against irradiation-induced DNA damage.ConclusionsBeyond 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.
Highlights
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
We find that some metal oxides increased radiation-induced radical formation (V2O5, for hydroxyl radicals; TiO2 for superoxides) while others were radioprotective
X-ray diffraction (XRD) confirmed the crystal phase identity of all NPs, except E u2O3 and Gd2O3 for which there was no close match in our database (Additional file 3: Figure S3)
Summary
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. Theoretical studies (McMahon et al 2016; Hwang et al 2017; Haume et al 2016; Roeske et al 2007) and experimental studies (Retif et al 2015; Liu et al 2018) have demonstrated that X-ray-induced radical formation can be greatly increased in the vicinity of nanoparticles of high atomic number (Z) elements, their oxides or sulphides [e.g. Ag: Liu et al (2016); Gd: Luchette et al (2014), Lux et al (2018); Hf: Marill et al (2014); Pt: Muhammad et al (2018); Au: Haume et al (2016), Rahman et al (2014); Bi: Algethami (2015), Sahu and Cates (2017)], which have large X-ray absorption cross sections and produce a shower of secondary electrons when irradiated For this reason, high atomic number nanoparticles have been the focus of nanoparticle radiosensitiser research, some of which are being clinically evaluated (Liu et al 2018), such as the Gd NP, AGuIX (Lux et al 2018) and the Hf NP, NBTXR3 (Marill et al 2014), both of which are currently in Phase II clinical trials (NCT03818386 and NCT03589339)
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