UV scintillating particles as radiosensitizer enhance cell killing after X-ray excitation

Publication date: Available online 29 June 2018
Source:Radiotherapy and Oncology
Author(s): Matthias Müller, Yimin Wang, Michael R. Squillante, Kathryn D. Held, R. Rox Anderson, Martin Purschke
Background and purposeRadiation therapy is the gold standard treatment for inoperable malignant tumors. However, due to the heterogeneity of the tumor, some regions are more radio resistant and can lead to metastasis and tumor recurrence. In this study, we propose combining traditional X-ray treatment with UVC-emitting LuPO4:Pr³⁺ nanoparticles (NPs) to increase the tumor control as well as to reduce tumor recurrence and metastasis. These NPs convert ionizing radiation into UVC-photons (UVC range: 200–280 nm) locally at the tumor site. Unlike X-ray, UVC-photons damage DNA directly via an oxygen-independent mechanism, which could improve treatment of radioresistant tumors such as hypoxic tumors.Materials and methodsThe effect of X-ray generated UVC-photons was tested on human fibroblasts incubated with NPs prior to radiation treatment. The surviving fraction of the cells was assessed by means of colony formation assay. Experiments were performed on normal and UVC sensitive cell lines to demonstrate the presence of UVC photons during treatment. In addition, UV-specific DNA damages were investigated using an immunofluorescence assay to measure cyclopyrimidine dimers (CPDs).ResultsCombined treatment showed an increased cell death of over 50%, compared to radiation alone. This results in a dose equivalent of 4 Gy for the combined treatment with 2 Gy irradiation. The formation of CPDs and the increased effect on UV sensitive cells indicate the presence of UV photons. The generated amount of CPDs is comparable to an UVC exposure of about 15 J × m⁻².ConclusionCombining NPs with ionizing radiation results in a localized dose surge, which could increase tumor control. It could also allow lowering the total applied dose to minimize unwanted side effects to the surrounding normal tissue while maintaining tumor control.



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