Abstract
Gold nanoparticles (GNPs) have been demonstrated as effective radiosensitizing agents in a range of preclinical models using broad field sources of various energies. This study aimed to distinguish between these mechanisms by applying subcellular targeting using a soft X-ray microbeam in combination with GNPs. DNA damage and repair kinetics were determined following nuclear and cytoplasmic irradiation using a soft X-ray (carbon K-shell, 278 eV) microbeam in MDA-MB-231 breast cancer and AG01522 fibroblast cells with and without GNPs. To investigate the mechanism of the GNP induced radiosensitization, GNP-induced mitochondrial depolarisation was quantified by TMRE staining, and levels of DNA damage were compared in cells with depolarised and functional mitochondria. Differential effects were observed following radiation exposure between the two cell lines. These findings were validated 24 hours after removal of GNPs by flow cytometry analysis of mitochondrial depolarisation. This study provides further evidence that GNP radiosensitisation is mediated by mitochondrial function and it is the first report applying a soft X-ray microbeam to study the radiobiological effects of GNPs to enable the separation of physical and biological effects.
Highlights
Gold nanoparticles (GNPs) have been demonstrated as effective radiosensitizing agents in a range of preclinical models using broad field sources of various energies
In order to assess the impact of Gold Nanoparticles (GNPs) on the DNA damage formation and repair, the 53BP 1 assay was used
Each plot highlights the impact of the presence of GNPs on the repair kinetic; data are corrected for non-irradiated controls
Summary
Gold nanoparticles (GNPs) have been demonstrated as effective radiosensitizing agents in a range of preclinical models using broad field sources of various energies. Interest in the use of radiotherapy contrast agents was stimulated by early studies finding elevated levels of damage in tissues after contrast enhanced medical imaging, indicating that the presence of a high-Z material can increase radiation damage[3] This is attributed to the high photoelectric cross-section of these materials which means that high Z materials absorb substantially more energy per unit mass than soft tissue (between 10–150 times for kV photons) and which translates to an increase in local dose[4]. While these dose enhancing effects were undesirable in imaging, there was interest in applying them to improve tumour cell killing in therapy. Calculations have suggested delivering 1% of gold by mass to the tumour would mean the doubling of the amount of energy deposited www.nature.com/scientificreports/
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