Cancer-selective, single agent chemoradiosensitising gold nanoparticles

PLoS One. 2017 Jul 10;12(7):e0181103. doi: 10.1371/journal.pone.0181103. eCollection 2017.

Abstract

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.

MeSH terms

  • Apoptosis / drug effects
  • Caspase Inhibitors / chemistry*
  • Caspase Inhibitors / pharmacology*
  • Cell Line
  • Cell Line, Tumor
  • Gold / chemistry*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Metal Nanoparticles / chemistry*
  • Microscopy, Electron, Transmission

Substances

  • Caspase Inhibitors
  • Gold

Grants and funding

Funding was provided by the European Union FP7-PEOPLE Initial Training Network “ARGENT – Advanced Radiotherapy, Generated by Exploiting Nanoprocesses and Technologies” Project ID 608163 http://itn-argent.eu. The funder provided support in the form of salary for SG, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. MR and PW are employees of Midatech Pharma. AS and RS-C are employees of GenesisCare. Neither of these companies provided financial support for this project. However, both companies were asked for their permission to publish. The specific roles of each author are articulated in the ‘author contributions’ section.