Radiation Biology

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SU_43_2432 - Investigating the radiosensitization effects of gold nanoparticles in combination with megavoltage radiation on U87 glioblastoma cells

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

Investigating the radiosensitization effects of gold nanoparticles in combination with megavoltage radiation on U87 glioblastoma cells
F. Kazmi1, K. A. Vallis2, M. L. K. Chua3, and B. Vellayappan4; 1National University Hospital, Singapore, Singapore, 2CRUK and MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom, 3National Cancer Centre Singapore, Singapore, Singapore, 4National University Cancer Institute (Singapore), Singapore, Singapore

Purpose/Objective(s): Gold nanoparticles (GNPs) have demonstrated great potential to be used as novel radiosensitizers. Despite significant dose enhancement observed in the presence of GNPs irradiated with orthovoltage x-rays, recent studies have shown inconsistent evidence of radiosensitization in the presence of GNPs with x-ray megavoltage energy (MV). This has been attributed to an underlying biological mechanism which is not well understood. To date, there have been no studies that have investigated the radiosensitization effects of GNP in U87 GBM with 6 MV x-rays. Our hypothesis is that U87 GBM cells incubated with 42nm GNPs will increase the DEF compared to non-GNP treated group when irradiated. Primary aim is to construct cell survival curves and calculate the DEF. Secondary aim is to understand the mechanism of radiosensitization by performing a Monte Carlo (MC) simulation and γ-H2AX assay.

Materials/Methods: Different concentrations of GNPs (50μg/mL and 100μg/mL) were incubated in U87 GBM cells and compared to U87 GBM cells alone. Intracellular uptake of GNPs was confirmed using dark field microscopy. Well plates were irradiated, using a LINAC (6 MV), at different doses (2Gy - 8Gy). Cytotoxicity and radiosensitization were evaluated by MTS-assay and multiple MTS-assay method, respectively. Primary cell survival curves were constructed and dose enhancement factor (DEF) calculated as a ratio of mean inactivation dose (MID) of GNPs treated group to U87 GBM cells alone. MC simulation was conducted, using toolkit Geant4, to determine the predictive dose in the nucleus with high concentration GNP and no GNP respectively, modelling our in vitro experiment. Finally, γ-H2AX immunofluorescence was performed and mean foci per cell was calculated in each group to assess for any increase in DNA double stranded break (DSB) in the presence of GNPs at 1 hour and 24 hours post irradiation (4Gy).

Results: Significant DEF of 1.12 (p = 0.0127) was observed in the 100μg/mL GNP group. No dose enhancement was observed in 50μg/mL GNP group, DEF of 1.04 (p = 0.221). Monte Carlo (MC) simulation demonstrated energy deposited in the nucleus between the non-GNP treated group and high concentration GNP group was 0.508 ±0.015 MeV and 0.556 ± 0.017 (p = 0.021). Based on MC, DEF of 1.09 ±0.07 (p<0.05) was achieved in the high concentration GNP group. γ-H2AX mean foci per cell was 51.25 ± 2.37 and 55.52 ± 2.41 (p=0.212) in the non-GNP treated group and 100μg/mL GNP group respectively at 1 hour post RT. At 24 hours post RT, mean foci per cell was 5.53 ±0.49 and 5.03 ± 0.53 (p>0.05) in the non-GNP treated group and 100μg/mL GNP group respectively.

Conclusion: GNPs, in high concentration, can cause significant radiosensitization in U87 GBM cells with MV x-ray. Our results indicate that the mechanism of enhancement is likely attributed to a physical dose deposition. The biological mechanism of radiosensitization may indeed be a secondary process, as a result of damage to critical organelles via dose deposition in close proximity of the irradiated GNPs.

Author Disclosure: F. Kazmi: None. K.A. Vallis: None. M.L. Chua: None. B. Vellayappan: None.

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