22 research outputs found
Cancer-selective, single agent chemoradiosensitising gold nanoparticles
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
MTH1 deficiency selectively increases non-cytotoxic oxidative DNA damage in lung cancer cells: more bad news than good?
Representative images of âCometsâ and the corresponding intensity profiles, showing (i) ~â5% Tail DNA damage, typical of the NSCLC cells treated with no siRNA or scramble siRNA, and analysed by regular Fpg-modified alkaline comet assay (0.8Â U Fpg/gel); and (ii) comets showing ~â10% tail DNA, typical of the NSCLC cells treated with MTH1 siRNA. Superimposed on the Comet images are the image analysis software (Komet 5.5, Andor Technology) determined boundaries demarcating the âComet headâ (pink circle) and âtail extentâ (vertical orange line) (Barber RC, Hickenbotham P, Hatch T, Kelly D, Topchiy N, Almeida GM, et al. Radiation-induced transgenerational alterations in genome stability and DNA damage. Oncogene. 2006;25(56):7336â7342). % tail DNAâ=â100 - % head DNA; % head DNAâ=â(integrated optical head intensity / (integrated optical head intensity + integrated optical tail intensity)) Ăâ100. (PDF 1431Â kb