An Evaluation of the Potential Radiosensitization Effect of Spherical Gold Nanoparticles to Induce Cellular Damage
Monique Engelbrecht-Roberts1,2, Xanthene Miles2, Charlot Vandevoorde3
1Department of Medical Bioscience, Faculty of Natural Sciences, University of the Western Cape, Cape Town 7535, South Africa.
Abstract:
Global disparities in cancer prevention, detection, and treatment demand a unified international effort to reduce the disease's burden and improve outcomes. Despite advances in chemotherapy and radiotherapy, many tumors remain resistant to these treatments. Gold nanoparticles (AuNPs) have shown promise as radiosensitizers, enhancing the effectiveness of low-energy X-rays by emitting Auger electrons that cause localized cellular damage. In this study, spherical AuNPs of 5 nm and 10 nm were characterized and tested on various cell lines, including malignant breast cells (MCF-7), non-malignant cells (CHO-K1 and MCF-10A), and human lymphocytes. Cells were treated with AuNPs and irradiated with attenuated 6 megavoltage (MV) X-rays or p(66)/Be neutron radiation to assess DNA double-strand break (DSB) damage, cell viability, and cell cycle progression. The combination of AuNPs and neutron radiation induced higher levels of γ-H2AX foci and micronucleus formation compared to treatments with AuNPs or X-ray radiation alone. AuNPs alone reduced cellular kinetics and increased the accumulation of cells in the G2/M phase, suggesting a block of cell cycle progression. For cell proliferation, significant effects were only observed at the concentration of 50 μg/mL of AuNPs, while lower concentrations had no inhibitory effect. Further research is needed to quantify internalized AuNPs and correlate their concentration with the observed cellular effects to unravel the biological mechanisms of their radioenhancement.
Insights
Gold nanoparticles (AuNPs) enhance neutron radiation therapy by increasing DNA damage and cell cycle arrest in cancer cells. Further studies are needed to optimize AuNP concentration for improved cancer treatment outcomes.
Area of Science:
- Nanotechnology
- Radiation Oncology
- Cancer Research
Background:
- Global cancer disparities necessitate novel therapeutic strategies.
- Tumor resistance to conventional chemotherapy and radiotherapy remains a significant challenge.
- Gold nanoparticles (AuNPs) show potential as radiosensitizers, enhancing radiation therapy efficacy.
Purpose of the Study:
- To investigate the radiosensitizing effects of gold nanoparticles (AuNPs) in combination with different radiation types.
- To evaluate the impact of AuNPs on DNA damage, cell viability, and cell cycle progression in various cell lines.
- To explore the potential of AuNPs for improving cancer treatment outcomes.
Main Methods:
- Characterization of 5 nm and 10 nm spherical AuNPs.
- Treatment of malignant (MCF-7) and non-malignant (CHO-K1, MCF-10A, lymphocytes) cell lines with AuNPs.
- Irradiation of cells using 6 MV X-rays or p(66)/Be neutron radiation.
- Assessment of DNA double-strand break (DSB) damage via γ-H2AX foci and micronucleus formation.
- Evaluation of cell viability, proliferation, and cell cycle progression.
Main Results:
- Combined AuNPs and neutron radiation significantly increased γ-H2AX foci and micronucleus formation compared to radiation or AuNPs alone.
- AuNPs alone induced cell cycle arrest at the G2/M phase and reduced cellular kinetics.
- Significant inhibition of cell proliferation was observed only at a high AuNP concentration (50 μg/mL).
Conclusions:
- AuNPs, particularly when combined with neutron radiation, demonstrate radiosensitizing properties by enhancing DNA damage and disrupting cell cycle progression.
- The study highlights the potential of AuNPs as an adjuvant therapy in radiation oncology.
- Further research is required to quantify AuNP uptake and establish concentration-dependent effects for clinical translation.
