Barium Titanate Nanoparticles Sensitise Treatment-Resistant Breast Cancer Cells to the Antitumor Action of Tumour-Treating Fields

Sci Rep. 2020 Feb 13;10(1):2560. doi: 10.1038/s41598-020-59445-x.

Abstract

Although tumour-treating fields (TTFields) is a promising physical treatment modality based on disruption of dipole alignments and generation of dielectrophoretic forces during cytokinesis, not much is known about TTFields-responsive sensitisers. Here, we report a novel TTFields-responsive sensitiser, barium titanate nanoparticles (BTNPs), which exhibit cytocompatibility, with non-cytotoxic effects on breast cancer cells. BTNPs are characterised by high dielectric constant values and ferroelectric properties. Notably, we found that BTNPs sensitised TTFields-resistant breast cancer cells in response to TTFields. In addition, BTNPs accumulated in the cytoplasm of cancer cells in response to TTFields. Further, we showed that TTFields combined with BTNPs exhibited antitumor activity by modulating several cancer-related pathways in general, and the cell cycle-related apoptosis pathway in particular. Therefore, our data suggest that BTNPs increase the antitumor action of TTFields by an electric field-responsive cytosolic accumulation, establishing BTNP as a TTFields-responsive sensitiser.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Barium Compounds / chemistry
  • Barium Compounds / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Proliferation / drug effects
  • Combined Modality Therapy
  • Drug Resistance, Neoplasm / drug effects*
  • Electric Stimulation Therapy
  • Female
  • Humans
  • MCF-7 Cells
  • Nanoparticles / chemistry*
  • Signal Transduction
  • Titanium / chemistry
  • Titanium / pharmacology*

Substances

  • Barium Compounds
  • barium titanate(IV)
  • Titanium