Proton beam-induced radiosensitizing effect of Ce$_{0.8}$Gd$_{0.2}$O$_{2-x}$ nanoparticles against melanoma cells in vitro

Proton beam therapy is being used increasingly to treat melanoma. Meanwhile, proton beam therapy has a number of disadvantages that can be reduced or completely eliminated through the use of modern innovative approaches, including the use of nanoradiosensitizers. Here we showed the possibility of using redox-active dextran-stabilized Ce$_{0.8}$Gd$_{0.2}$O$_{2-x}$ nanoparticles (Ce$_{0.8}$Gd$_{0.2}$O$_{2-x}$ NPs) as a radiosensitizer to promote mouse melanoma cell death under proton beam irradiation in vitro. It has been shown that these Ce$_{0.8}$Gd$_{0.2}$O$_{2-x}$ NPs do not reduce the viability and survival rate of both NCTC L929 normal mouse fibroblasts and B16/F10 mouse melanoma cells in a wide range of concentrations. However, Ce$_{0.8}$Gd$_{0.2}$O$_{2-x}$ NPs significantly reduce the mitochondrial membrane potential of these cells. Additionally, it has been shown that Ce$_{0.8}$Gd$_{0.2}$O$_{2-x}$ NPs are able to effectively reduce the clonogenic activity of B16/F10 melanoma cells under proton beam irradiation. Meanwhile, proton beam irradiation remarkably reduced the clonogenic activity and MMP of melanoma cells. Hence, Ce$_{0.8}$Gd$_{0.2}$O$_{2-x}$ NPs act as a radiosensitizer in B16/F10 mouse melanoma cells under proton beam irradiation. We assume that such radiosensitizing effect of Ce$_{0.8}$Gd$_{0.2}$O$_{2-x}$ NPs is due to a decrease of the membrane mitochondrial potential. Thus, the use of Ce$_{0.8}$Gd$_{0.2}$O$_{2-x}$ NPs in combination with proton beam irradiation is a promising approach for the effective treatment of melanoma.