Enhancement of radiotherapy by ceria nanoparticles modified with neogambogic acid in breast cancer cells

Abstract

Feng Chen,1 Xiao Hong Zhang,1 Xiao Dan Hu,1 Wei Zhang,1 Zhi Chao Lou,1 Li Hua Xie,1 Pei Dang Liu,2 Hai Qian Zhang1,21College of Materials Science and Technology, Nanjing University of Aeronautics and Astronautics, 2Jiangsu Laboratory for Biomaterials and Devices, Southeast University, Nanjing, People’s Republic of ChinaAbstract: Radiotherapy is one of the main strategies for cancer treatment but has significant challenges, such as cancer cell resistance and radiation damage to normal tissue. Radiosensitizers that selectively increase the susceptibility of cancer cells to radiation can enhance the effectiveness of radiotherapy. We report here the development of a novel radiosensitizer consisting of monodispersed ceria nanoparticles (CNPs) covered with the anticancer drug neogambogic acid (NGA-CNPs). These were used in conjunction with radiation in MCF-7 breast cancer cells, and the efficacy and mechanisms of action of this combined treatment approach were evaluated. NGA-CNPs potentiated the toxic effects of radiation, leading to a higher rate of cell death than either treatment used alone and inducing the activation of autophagy and cell cycle arrest at the G2/M phase, while pretreatment with NGA or CNPs did not improve the rate of radiation-induced cancer cells death. However, NGA-CNPs decreased both endogenous and radiation-induced reactive oxygen species formation, unlike other nanomaterials. These results suggest that the adjunctive use of NGA-CNPs can increase the effectiveness of radiotherapy in breast cancer treatment by lowering the radiation doses required to kill cancer cells and thereby minimizing collateral damage to healthy adjacent tissue.Keywords: ceria nanoparticles, radiotherapy, breast cancer cells, neogambogic acid, radiosensitization