PLoS ONE (Jan 2017)

Cancer-selective, single agent chemoradiosensitising gold nanoparticles.

  • Sophie Grellet,
  • Konstantina Tzelepi,
  • Meike Roskamp,
  • Phil Williams,
  • Aquila Sharif,
  • Richard Slade-Carter,
  • Peter Goldie,
  • Nicky Whilde,
  • Małgorzata A Śmiałek,
  • Nigel J Mason,
  • Jon P Golding

DOI
https://doi.org/10.1371/journal.pone.0181103
Journal volume & issue
Vol. 12, no. 7
p. e0181103

Abstract

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Two nanometre gold nanoparticles (AuNPs), bearing sugar moieties and/or thiol-polyethylene glycol-amine (PEG-amine), were synthesised and evaluated for their in vitro toxicity and ability to radiosensitise cells with 220 kV and 6 MV X-rays, using four cell lines representing normal and cancerous skin and breast tissues. Acute 3 h exposure of cells to AuNPs, bearing PEG-amine only or a 50:50 ratio of alpha-galactose derivative and PEG-amine resulted in selective uptake and toxicity towards cancer cells at unprecedentedly low nanomolar concentrations. Chemotoxicity was prevented by co-administration of N-acetyl cysteine antioxidant, or partially prevented by the caspase inhibitor Z-VAD-FMK. In addition to their intrinsic cancer-selective chemotoxicity, these AuNPs acted as radiosensitisers in combination with 220 kV or 6 MV X-rays. The ability of AuNPs bearing simple ligands to act as cancer-selective chemoradiosensitisers at low concentrations is a novel discovery that holds great promise in developing low-cost cancer nanotherapeutics.