Synergistically Enhancing the Therapeutic Effect of Radiation Therapy with Radiation Activatable and Reactive Oxygen Species-Releasing Nanostructures

ACS Nano. 2018 May 22;12(5):4946-4958. doi: 10.1021/acsnano.8b02038. Epub 2018 May 3.

Abstract

Nanoparticle-based radio-sensitizers can amplify the effects of radiation therapy on tumor tissue even at relatively low concentrations while reducing the potential side effects to healthy surrounding tissues. In this study, we investigated a hybrid anisotropic nanostructure, composed of gold (Au) and titanium dioxide (TiO2), as a radio-sensitizer for radiation therapy of triple-negative breast cancer (TNBC). In contrast to other gold-based radio sensitizers, dumbbell-like Au-TiO2 nanoparticles (DATs) show a synergistic therapeutic effect on radiation therapy, mainly because of strong asymmetric electric coupling between the high atomic number metals and dielectric oxides at their interfaces. The generation of secondary electrons and reactive oxygen species (ROS) from DATs triggered by X-ray irradiation can significantly enhance the radiation effect. After endocytosed by cancer cells, DATs can generate a large amount of ROS under X-ray irradiation, eventually inducing cancer cell apoptosis. Significant tumor growth suppression and overall improvement in survival rate in a TNBC tumor model have been successfully demonstrated under DAT uptake for a radio-sensitized radiation therapy.

Keywords: gold-titanium oxide nanoparticles; heterogeneous interface; radiation/chemotherapy; radio sensitizer; reactive oxygen species; triple-negative breast cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Biocompatible Materials / chemistry
  • Cell Line, Tumor
  • Cell Survival
  • Female
  • Gold / chemistry*
  • Humans
  • Metal Nanoparticles / chemistry*
  • Mice, Nude
  • Neoplasm Transplantation
  • Polyethylene Glycols / chemistry
  • Radiation-Sensitizing Agents / chemistry*
  • Radiation-Sensitizing Agents / therapeutic use
  • Reactive Oxygen Species / metabolism*
  • Tissue Distribution
  • Titanium / chemistry*
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / radiotherapy*

Substances

  • Biocompatible Materials
  • Radiation-Sensitizing Agents
  • Reactive Oxygen Species
  • titanium dioxide
  • Polyethylene Glycols
  • Gold
  • Titanium