Titanium oxide nano-radiosensitizers for hydrogen peroxide delivery into cancer cells

Polyacrylic acid-modified titanium peroxide nanoparticles (PAA-TiO_x NPs) are promising radiosensitizers that enhance the therapeutic effect of X-ray irradiation after local injection into tumors. However, the mechanism for this reaction has remained unclear with the exception of the involvement of hydrogen peroxide (H₂O₂), which is released by PAA-TiO_x NPs to a liquid phase during dispersion. In the present study, a clonogenic assay was used to compare PAA-TiO_x NPs with free H₂O₂ molecules to investigate the effect exerted on the radiosensitivity of cancer cells in vitro. A cell-free dialysis method revealed that a portion of the H₂O₂ adsorbed onto the PAA-TiO_x NPs during synthesis could be released during a treatment regimen. The H₂O₂ release lasted for 7 h, which was sufficient for one radiation treatment procedure. For in vitro experiments, cultured human pancreatic cancer cells took up PAA-TiO_x NPs in 10 min after administration. Interestingly, when the cells were washed with a buffer after treatment with either a PAA-TiO_x NP or H₂O₂ solution, the intracellular H₂O₂ levels remained higher with PAA-TiO_x NP treatment compared with the H₂O₂ solution treatment. Furthermore, the effects of subsequent X-ray irradiation corresponded to the intracellular H₂O₂ levels. These results indicate that PAA-TiO_x NPs are efficient carriers of H₂O₂ into cancer cells and thus enhance the radiosensitivity.