Combination of gold nanoparticles with low-LET irradiation: an approach to enhance DNA DSB induction in HT29 colorectal cancer stem-like cells
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High-linear energy transfer (high LET) irradiation has significant cytotoxic effects on different cancerous stem-like cells (CSLCs) such as colorectal CSLCs. A review of the literature has indicated that the presence of gold nanoparticles (GNPs) enables low-LET irradiation to produce highly non-homogeneous dose distributions like high-LET irradiation. The purpose of this study was to evaluate the radioresponsiveness of HT29 colorectal CSLCs under low-LET irradiation (X-ray) and in the presence of GNPs.
Radioresponsiveness was evaluated using the ϒ-H2AX foci formation assay, the clonogenic assay, the cell cycle progression assay and analyses of radiobiological parameters.
In the presence of GNPs, the survival fraction of HT29 CSLCs was significantly reduced and caused significant changes in the radiobiological parameters after irradiation. In addition, ϒ-H2AX assay showed that in the presence of GNPs, the persistent DNA double-strand breaks were significantly increased in irradiated HT29 CSLCs. The relative biological effectiveness value of GNPs with X-rays was about 1.6 for HT-29 CSLCs at the 10% of cell survival fraction (D10 level) when compared to X-rays alone.
Therefore, the combination of GNPs with X-ray irradiation has the potential to kill HT29 CSLCs greater than the X-ray alone, and may be considered as an alternative for high-LET irradiation.
KeywordsCancer stem-like cell Gold nanoparticle DNA DSBs RBE value
The authors are highly thankful to all technicians who provided support during the course of research. The part of this work was supported by Stem Cell Research Center, Golestan University of Medical Science (Grant no: 950818185).
ABZ and AM designed the research. ABZ, AM and BA performed the experiments. ABZ, AM, and LDA contributed to analysis and interpretation of data. AM and ABZ wrote the manuscript. All authors reviewed the manuscript.
Compliance with ethical standards
Conflict of interest
The author(s) declare no competing interests.
This article does not contain any studies with human participants or animals performed by any of the authors.
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