Au-Pt Nanoparticle Formulation as a Radiosensitizer for Radiotherapy with Dual Effects

Int J Nanomedicine. 2021 Jan 12:16:239-248. doi: 10.2147/IJN.S287523. eCollection 2021.

Abstract

Background: Radiotherapy occupies an essential position as one of the most significant approaches for the clinical treatment of cancer. However, we cannot overcome the shortcoming of X-rays which is the high value of the oxygen enhancement ratio (OER). Radiosensitizers with the ability to enhance the radiosensitivity of tumor cells provide an alternative to changing X-rays to protons and heavy ion radiotherapy.

Materials and methods: We prepared the Au-Pt nanoparticles (Au-Pt NPs) using a one-step method. The characteristics of the Au-Pt NPs were determined using TEM, HAADF-STEM, elemental mapping images, and DLS. The enhanced radiotherapy was demonstrated in vitro using MTT assays, colony formation assays, fluorescence imaging, and flow cytometric analyses of the apoptosis. The biodistribution of the Au-Pt NPs was analyzed using ICP-OES, and thermal images. The enhanced radiotherapy was demonstrated in vitro using immunofluorescence images, tumor volume and weigh, and hematoxylin & eosin (H&E) staining.

Results: Polyethylene glycol (PEG) functionalized nanoparticles composed of the metallic elements Au and Pt were designed to increase synergistic radiosensitivity. The mechanism demonstrated that heavy metal NPs possess a high X-ray photon capture cross-section and Compton scattering effect which increased DNA damage. Furthermore, the Au-Pt NPs exhibited enzyme-mimicking activities by catalyzing the decomposition of endogenous H2O2 to O2 in the solid tumor microenvironment (TME).

Conclusion: Our work provides a systematically administered radiosensitizer that can selectively reside in a tumor via the EPR effect and enhances the efficiency of treating cancer with radiotherapy.

Keywords: TME; nano-enzyme; radiosensitizer; radiotherapy.

MeSH terms

  • Animals
  • Catalysis
  • Cell Line, Tumor
  • Cell Survival
  • Female
  • Gold / therapeutic use*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Metal Nanoparticles / chemistry*
  • Metal Nanoparticles / ultrastructure
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms / radiotherapy*
  • Platinum / therapeutic use*
  • Radiation-Sensitizing Agents / pharmacokinetics
  • Radiation-Sensitizing Agents / therapeutic use*
  • Tissue Distribution
  • Tumor Microenvironment

Substances

  • Radiation-Sensitizing Agents
  • Platinum
  • Gold