Study On The Radiotherapy Sensitization Effect And Mechanism On U251 Cells By Fe₃O₄@Ag Nanoparticles

Radiation therapy is one of the main treatments for cancer,but the resistance of cancer cells to radiation can hinder the effect of radiotherapy.Therefore,an efficient radiosensitizer is urgently needed to overcome this radiation resistance.With the development of biomedical nanotechnology,many nanomaterials have also been demonstrated to be useful as radiosensitizers.The radiosensitizing effect of silver nanoparticles has long been concerned by us;magnetic nanoparticles not only have certain radiosensitizing sensitivities,but also can be used as magnetic hyperthermia,photothermiotherapy and targeted positionin,and have great prospects in application.Therefore,based on the radiosensitization ability of nano-silver and magnetic nanoparticles,a novel core-shell structure of Fe₃O₄@Ag nanoparticles was prepared,and its radiosensitizing effect on glioma U251 cells was explored.Look for a highly effective radiotherapy sensitizer.The research contents of this paper are as follows:The radiosensitizing effect of Fe₃O₄@Ag nanoparticles on U251 cells was evaluated by clone formation experiments;the inhibition of U251 cells treated with Fe₃O₄@Ag nanoparticles proliferation at different time points after irradiation was observed by inverted fluorescence microscope;the dynamic changes of autophagy and apoptosis were analyzed,and the concentrations of reactive oxygen species,caspase-3,cell cycle and calcium ions were detected by flow cytometry;the mechanism of sensitization was further analyzed by using 3-MA and BAPTA-AM to inhibit autophagy levels and calcium ion concentrations,respectively;the DNA damage induced by U251 cells was evaluated and compared with Fe₃O₄@Ag,Fe₃O₄-OA and Ag nanoparticles combined with X-rays using Geant4 simulation software.The results of this paper show that Fe₃O₄@Ag nanoparticles have the highest ability of radiosensitization among the three nanoparticles（SER=1.80）,the underlying mechanism of Fe₃O₄@Ag nanoparticles’radiosensitivity enhancement is not iron death,but through decrease of the cytoprotective autophagy at the early stage,and increase of the calcium-dependent apoptosis at the later stage,and deposition of energy in the nucleus causes DNA breaks.In this thesis,the radiosensitizing effect of Fe₃O₄@Ag nanoparticles was studied,and its sensitizing mechanism was discussed.It provides a theoretical basis for the potential application of Fe₃O₄@Ag nanoparticles as radiosensitizers in the treatment of glioma cells.