Enhanced radiation efficiency by gold nanoparticles after proton beam irradiation in medulloblastoma cell lines

Introduction: In pediatric oncology, one quarter of patients is diagnosed with a tumor of the CNS. Although outcome did improve significantly during the last decade, prognosis of malignant CNS-tumors in childhood is still lagging behind and needs further improvement. Especially for relapse patients, prognosis is worse and curative therapy approaches are missed. Besides radical resection and chemotherapy, radiotherapy is standard of care. However, secondary malignancy after treatment of CNS-tumors in childhood occurs in 5.5% of cases, thus accounting for 19% of all secondary cancers in childhood tumors. Although proton beam irradiation allows to cover target volumes comparable to those achieved by photons, the main advantage of proton beams is sparing of healthy tissues. Recent in vitro and in vivo studies demonstrated an enhanced biological effect of proton therapy in the presence of gold nanoparticles. This held true both for irradiated cancer cells in vitro and in vivo. In this study we wanted to extend these findings to preclinical medulloblastoma models using proton beams and well-defined gold nanoparticles. Materials and methods: Three different medulloblastoma cell lines (DAOY, ONS76 and UW228) were cultured and treated with proton beam irradiation after incubation with gold nanoparticles or without. Three different doses of irradiation (6, 10 and 20 Gy) were evaluated. Stock solutions of gold nanoparticles were used in serial dilutions. Viability of medulloblastoma cells was evaluated by using MTT assays 72 hours after irradiation. Results: As expected, proton beam irradiation had the main effect on medulloblastoma cell viability. However, in our study gold nanoparticles had a cytotoxic effect at high concentrations (> 400 µg/ml). Proton beam irradiation in the presence of gold nanoparticles decreased the IC50 that was observed when cells were irradiated only. Conclusion: Confirming published data we could show enhanced biological effectiveness of proton beam irradiation in medulloblastoma cell lines in the presence of gold nanoparticles. Sensitization was directly correlated with radiation dose and the amount of gold nanoparticles per cell. Further investigation on the impact of particle size on toxicity as well as on enhanced radiation efficiency is needed.