Gold nanoparticles have been shown to enhance radiation doses delivered to biological targets due to the high absorption coefficient of gold atoms, stemming from their high atomic number (Z) and physical density. These properties significantly increase the likelihood of photoelectric effects and Compton scattering interactions. Gold nanoparticles are a novel radiosensitizing agent that can potentially be used to increase the effectiveness of current radiation therapy techniques and improve the diagnosis and treatment of cancer. However, the optimum radiosensitization effect of gold nanoparticles is strongly dependent on photon energy, which theoretically is predicted to occur in the kilovoltage range of energy. In this research, synchrotron-generated monoenergetic X-rays in the 30–100 keV range were used to investigate the energy dependence of radiosensitization by gold nanoparticles and also to determine the photon energy that produces optimum effects. This investigation was conducted using cells in culture to measure dose enhancement. Bovine aortic endothelial cells with and without gold nanoparticles were irradiated with X-rays at energies of 30, 40, 50, 60, 70, 81, and 100 keV. Trypan blue exclusion assays were performed after irradiation to determine cell viability. Cell radiosensitivity enhancement was indicated by the dose enhancement factor which was found to be maximum at 40 keV with a value of 3.47. The dose enhancement factor obtained at other energy levels followed the same direction as the theoretical calculations based on the ratio of the mass energy absorption coefficients of gold and water. This experimental evidence shows that the radiosensitization effect of gold nanoparticles varies with photon energy as predicted from theoretical calculations. However, prediction based on theoretical assumptions is sometimes difficult due to the complexity of biological systems, so further study at the cellular level is required to fully characterize the effects of gold nanoparticles with ionizing radiation.

Objective: Radiosensitisation caused by titanium dioxide nanoparticles (TiO₂-NPs) is investigated using phantoms (PRESAGE^® dosimeters) and in vitro using two types of cell lines, cultured human keratinocyte (HaCaT) and prostate cancer (DU145) cells.

Gold nanoparticles (AuNP) can increase the efficacy of radiation therapy by sensitising tumor cells to radiation damage. When used in combination with radiation, AuNPs enhance the rate of cell killing; hence, they may be of great value in radiotherapy. This study assessed the effects of radiation and AuNPs on mitochondrial reactive oxygen species (ROS) generation in cancer cells as an adjunct therapeutic target in addition to the DNA of the cell. Mitochondria are considered one of the primary sources of cellular ROS. High levels of ROS can result in an intracellular state of oxidative stress, leading to permanent cell damage. In this study, human melanoma and prostate cancer cell lines, with and without AuNPs, were irradiated with 6-Megavolt X-rays at doses of 0–8 Gy. Indicators of mitochondrial stress were quantified using two techniques, and were found to be significantly increased by the inclusion of AuNPs in both cell lines. Radiobiological damage to mitochondria was quantified via increased ROS activity. The ROS production by mitochondria in cells was enhanced by the inclusion of AuNPs, peaking at ~4 Gy and then decreasing at higher doses. This increased mitochondrial stress may lead to more effectively kill of AuNP-treated cells, further enhancing the applicability of functionally-guided nanoparticles.

Purpose: The purpose of this study was to determine dose enhancement (DE) and the possible clinical benefits associated with the inclusion of gold nanoparticles (AuNPs) in cancer cells irradiated by either an ¹⁹²Ir brachytherapy source or a Xoft^® Axxent^® Electronic (eBx™) Brachytherapy. Patients and methods: Brachytherapy DE caused by AuNPs is investigated using two methods, namely ¹⁹²Ir and eBx™ Brachytherapy. The second method, which was recently introduced clinically, operates at ~50 kV, which is also the optimal beam energy for DE. In this in vitro study, two cancer cell lines, lung (A549) and prostate (DU145), were used. Cells were incubated with 1 mM (2% w/w) concentration of AuNPs of ~15 nm in size. The control groups were exposed to a range of doses from 0 (control) to 6 Gy, with eBx™ and ¹⁹²Ir sources separately. A clonogenic assay was conducted to determine cell survival curves. Results: High dose enhancement factor (DEF) values were achieved in treated groups with low concentration of AuNPs with the 50 kV energy associated with the eBx™. The DE levels in eBx™ for Du145 and A549 cells were found to be 2.90 and 2.06, respectively. The results showed DEFs measured for the same cell lines using ¹⁹²Ir brachytherapy to be 1.67 and 1.54 for Du145 and A549 cancer cells, respectively. This clearly indicates that much higher DE values are obtained in the case of eBx™ X-ray brachytherapy compared to ¹⁹²Ir gamma brachytherapy. Conclusion: The higher DE values obtained with eBx™ compared to ¹⁹²Ir brachytherapy can be attributed to the lower average energy of the former and being closer to the optimal energy for DE. This could potentially be utilized by medical practitioners and clinicians to achieve the same tumor control with a significantly lower dose from the eBx™ compared to the ¹⁹²Ir brachytherapy treatment, thus bringing huge benefits to the brachytherapy-treated patients.

The effect of 15 nm-sized gold nanoparticles (AuNPs) and/or ionizing radiation (IR) on the migration and adhesion of human prostate (DU145) and lung (A549) cancer cell lines was investigated. Cell migration was measured by observing the closing of a gap created by a pipette tip on cell monolayers grown in 6-well plates. The ratio of the gap areas at 0 h and 24 h were used to calculate the relative migration. The relative migration of cells irradiated with 5 Gy was found to be 89% and 86% for DU145 and A549 cells respectively. When the cells were treated with 1 mM AuNPs this fell to ~75% for both cell lines. However, when the cells were treated with both AuNPs and IR an additive effect was seen, as the relative migration rate fell to ~60%. Of interest was that when the cells were exposed to either 2 or 5 Gy IR, their ability to adhere to the surface of a polystyrene culture plate was significantly enhanced, unlike that seen for AuNPs. The delays in gap filling (cell migration) in cells treated with IR and/or AuNPs can be attributed to cellular changes which also may have altered cell motility. In addition, changes in the cytoskeleton of the cancer cells may have also affected adhesiveness and thus the cancer cell’s motility response to IR.