A GdW10@PDA-CAT Sensitizer with High-Z Effect and Self-Supplied Oxygen for Hypoxic-Tumor Radiotherapy

Molecules. 2021 Dec 26;27(1):128. doi: 10.3390/molecules27010128.

Abstract

Anticancer treatment is largely affected by the hypoxic tumor microenvironment (TME), which causes the resistance of the tumor to radiotherapy. Combining radiosensitizer compounds and O2 self-enriched moieties is an emerging strategy in hypoxic-tumor treatments. Herein, we engineered GdW10@PDA-CAT (K3Na4H2GdW10O36·2H2O, GdW10, polydopamine, PDA, catalase, CAT) composites as a radiosensitizer for the TME-manipulated enhancement of radiotherapy. In the composites, Gd (Z = 64) and W (Z = 74), as the high Z elements, make X-ray gather in tumor cells, thereby enhancing DNA damage induced by radiation. CAT can convert H2O2 to O2 and H2O to enhance the X-ray effect under hypoxic TME. CAT and PDA modification enhances the biocompatibility of the composites. Our results showed that GdW10@PDA-CAT composites increased the efficiency of radiotherapy in HT29 cells in culture. This polyoxometalates and O2 self-supplement composites provide a promising radiosensitizer for the radiotherapy field.

Keywords: O2 self-supplement; catalase; polyoxometalates; radiosensitizer; radiotherapy.

MeSH terms

  • Anions / chemistry
  • Biocompatible Materials / chemistry
  • Catalase / metabolism
  • Cell Line, Tumor
  • Gadolinium / chemistry*
  • HT29 Cells
  • Humans
  • Hydrogen Peroxide / metabolism
  • Indoles / chemistry
  • Nanocomposites / chemistry*
  • Oxygen / metabolism
  • Polyelectrolytes / chemistry
  • Polymers / chemistry
  • Radiation-Sensitizing Agents / chemistry*
  • Radiation-Sensitizing Agents / pharmacology
  • Reactive Oxygen Species / metabolism
  • Tumor Hypoxia / radiation effects*
  • Tumor Microenvironment
  • Tungsten / chemistry*

Substances

  • Anions
  • Biocompatible Materials
  • Indoles
  • Polyelectrolytes
  • Polymers
  • Radiation-Sensitizing Agents
  • Reactive Oxygen Species
  • polydopamine
  • polyoxometalate
  • Gadolinium
  • Hydrogen Peroxide
  • Catalase
  • Oxygen
  • Tungsten