Elham Shahhoseini

It has been shown lately that gold nanoparticles (AuNPs) and ionizing radiation (IR) have inhibitory effects on cancer cell migration while having promoting effects on normal cells' motility. Also, IR increases cancer cell adhesion with no significant effects on normal cells. In this study, synchrotron-based microbeam radiation therapy, as a novel pre-clinical radiotherapy protocol, is employed to investigate the effects of AuNPs on cell migration. Experiments were conducted utilizing synchrotron X-rays to investigate cancer and normal cell morphology and migration behaviour when they are exposed to synchrotron broad beams (SBB) and synchrotron microbeams (SMB). This in vitro study was conducted in two phases. In phase I two cancer cell lines – human prostate (DU145) and human lung (A549) – were exposed to various doses of SBB and SMB. Based on the phase I results, in phase II two normal cell lines were studied: human epidermal melanocytes (HEM) and human primary colon epithelial (CCD841), along with their respective cancerous counterparts, human primary melanoma (MM418-C1) and human colorectal adenocarcinoma (SW48). The results show that radiation-induced damage in cells' morphology becomes visible with SBB at doses greater than 50 Gy, and incorporating AuNPs increases this effect. Interestly, under the same conditions, no visible morphological changes were observed in the normal cell lines post-irradiation (HEM and CCD841). This can be attributed to the differences in cell metabolic and reactive oxygen species levels between normal and cancer cells. The outcome of this study highlights future applications of synchrotron-based radiotherapy, where it is possible to deliver extremely high doses to cancer tissues whilst preserving surrounding normal tissues from radiation-induced damage.

This study examined the effects of gold nanoparticles (AuNPs) and/or ionizing radiation (IR) on the viability and motility of human primary colon epithelial (CCD841) and colorectal adenocarcinoma (SW48) cells as well as human primary epidermal melanocytes (HEM) and melanoma (MM418-C1) cells. AuNPs up to 4 mM had no effect on the viability of these cell lines. The viability of the cancer cells was ~60% following exposure to 5 Gy. Exposure to 5 Gy X-rays or 1 mM AuNPs showed the migration of the cancer cells ~85% that of untreated controls, while co-treatment with AuNPs and IR decreased migration to ~60%. In the non-cancerous cell lines gap closure was enhanced by ~15% following 1 mM AuNPs or 5 Gy treatment, while for co-treatment it was ~22% greater than that for the untreated controls. AuNPs had no effect on cell re-adhesion, while IR enhanced only the re-adhesion of the cancer cell lines but not their non-cancerous counterparts. The addition of AuNPs did not enhance cell adherence. This different reaction to AuNPs and IR in the cancer and normal cells can be attributed to radiation-induced adhesiveness and metabolic differences between tumour cells and their non-cancerous counterparts.

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.

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.