Cancer-selective, single agent chemoradiosensitising gold nanoparticles.
Sophie GrelletKonstantina TzelepiMeike RoskampPhil WilliamsAquila SharifRichard Slade-CarterPeter GoldieNicky WhildeMałgorzata A ŚmiałekNigel J MasonJon P GoldingPublished in: PloS one (2017)
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.
Keyphrases
- gold nanoparticles
- papillary thyroid
- induced apoptosis
- squamous cell
- oxidative stress
- low cost
- drug delivery
- squamous cell carcinoma
- cell death
- gene expression
- childhood cancer
- computed tomography
- magnetic resonance imaging
- cell cycle arrest
- intensive care unit
- liver failure
- signaling pathway
- respiratory failure
- acute respiratory distress syndrome
- extracorporeal membrane oxygenation
- aortic dissection
- fluorescent probe
- contrast enhanced