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

Kenta Morita; Yuya Nishimura; Satoko Nakamura; Yuki Arai; Chiya Numako; Kazuyoshi Sato; Masao Nakayama; Hiroaki Akasaka; Ryohei Sasaki; Chiaki Ogino; Akihiko Kondo

doi:10.1016/j.colsurfb.2020.111451

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

Colloids Surf B Biointerfaces. 2021 Feb:198:111451. doi: 10.1016/j.colsurfb.2020.111451. Epub 2020 Nov 7.

Authors

Affiliations

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: ochiaki@port.kobe-u.ac.jp.
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.

PMID: 33223346
DOI: 10.1016/j.colsurfb.2020.111451

Abstract

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.

Keywords: Drug delivery system; Hydrogen peroxide; Radiosensitization; Radiotherapy; Titanium oxide nanoparticle.

MeSH terms

Humans
Hydrogen Peroxide
Nanoparticles*
Neoplasms*
Radiation-Sensitizing Agents*
Titanium

Substances

Radiation-Sensitizing Agents
titanium dioxide
Hydrogen Peroxide
Titanium