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

Affiliation

Morita K(1), Nishimura Y(2), Nakamura S(2), Arai Y(3), Numako C(3), Sato K(4), Nakayama M(5), Akasaka H(5), Sasaki R(5), Ogino C(6), Kondo A(7).
Author information:
(1)Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, Rokkodaicho 1-1, Nada-ku, Kobe 657-8501, Japan; Research Facility Center for Science and Technology, Kobe University, Rokkodaicho 1-1, Nada-ku, Kobe 657-8501, Japan.
(2)Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, Rokkodaicho 1-1, Nada-ku, Kobe 657-8501, Japan.
(3)Graduate School of Science, Chiba University, 1-33, Yayoi, Inage, Chiba, 263-8522, Japan.
(4)Division of Environmental Engineering Science, Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjincho, Kiryu, Gunma, 376-8515, Japan.
(5)Division of Radiation Oncology, Kobe University Graduate School of Medicine, Kusunokicho 7-5-2, Chuou-ku, Kobe 650-0017, Japan.
(6)Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, Rokkodaicho 1-1, Nada-ku, Kobe 657-8501, Japan. Electronic address: [Email]
(7)Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, Rokkodaicho 1-1, Nada-ku, Kobe 657-8501, Japan; Organization of Advanced Science and Technology, Kobe University, Rokkodaicho 1-1, Nada-ku, Kobe 657-8501, Japan.

Abstract

Polyacrylic acid-modified titanium peroxide nanoparticles (PAA-TiOx 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-TiOx NPs to a liquid phase during dispersion. In the present study, a clonogenic assay was used to compare PAA-TiOx 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-TiOx 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-TiOx NPs in 10 min after administration. Interestingly, when the cells were washed with a buffer after treatment with either a PAA-TiOx NP or H2O2 solution, the intracellular H2O2 levels remained higher with PAA-TiOx 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-TiOx NPs are efficient carriers of H2O2 into cancer cells and thus enhance the radiosensitivity.