A Comparative Study Of The Radiosensitizing Effects Of Gold And Silver Nanoparticles On Glioma

Background and Objective:Malignant glioma is the most common primary intracranial tumor and is among the top ten cancers for mortality. Radiotherapy performs an important function in glioma treatment, but resistance to radiation of most glioma cells limits the therapeutic efficacy of this standard adjuvant treatment. Though increasing the radiation dose can effectively decimate tumor cells, it also cause serious harm to surrounding normal tissues. Thus, how to improve the effect of radiotherapy on glioma cells is still a key problem to be solved. In recent years, with the rapid development of nanotechnology, nano-sized materials as novel radiosensitizers open a new chapter in cancer radiotherapy history. Among these nanomaterials, gold nanoparticles (AuNPs) are receiving much attention owing to their attractive properties, such as good biocompatibility, chemical stability, ease of surface modification, and high X-ray absorption coefficients. A number of studies have revealed that the biological mechanisms of AuNPs radiosensitization are involved in cell cycle arrest and oxidative stress mediated apoptosis, necrosis or DNA damage.The effectiveness of AuNPs as a potential radiosensitizer has been determined in a range of cancer cell lines, animal models and radiation sources. However, whether AuNPs can also sensitize glioma cells to radiation at clinically relevant megavoltage (MV) energies is still unclear. Silver nanoparticles (AgNPs) have broad application prospects in the field of biomedicine due to their unique antibacterial, catalytic and anticancer properties. Previous studies by our group demonstrated the radiosensitizing effect of AgNPs on glioma both in vitro and in vivo. Moreover, the enhanced radiation effects of silver nanomaterials were also observed in other different cancer cell lines. In order to determine that between these two most intensively studied nano-radiosensitizers which is more effective in terms of a radiosensitizing effect, we will synthesize AuNPs and AgNPs with similar size using sodium citrate reduction system, evaluate and compare their in vitro and in vivo therapeutic efficacies combined with 6 MV X-ray radiation on glioma at the same mass and molar concentrations. These findings will provide an important experimental and theoretical basis for selecting and applying highly effective nano-radiosensitizer for the treatment of glioma.Methods:(1) Characterization of nanoparticles:AuNPs and AgNPs were synthesized by sodium citrate reduction method and characterized by TEM, UV-Vis, ICP-MS and DLS.(2) In virto:Cell viability and radiosensitizing effects of AuNPs and AgNPs on glioma cells were detected by CCK8 and colony-forming assay, respectively. Cell apoptosis and death were tested by flow cytometry and Hoechst-PI double staining, respectively. Cell autophagy was examined by acridine orang, monodansylcadaverine and LC3II immunofluorescence staining.(3) In vivo:The in vivo anti-glioma efficacy of AuNPs and AgNPs, which were intratumorally administered, in combination with a single dose of ionizing radiation was evaluated by an orthotopic mouse brain tumor model. The survival time of glioma-bearing mice was recorded and used in the survival analysis.Results:(1) AuNPs and AgNPs showed good monodispersity with an average size of 15 nm. (2) In vitro:The combination of AuNPs and AgNPs with radiation could decrease the viability of glioma cells in a dose dependent manner, with the latter being stronger. The enhancement ratios of the same molar concentration of AgNPs, AuNPs and the same mass concentration of AgNPs were 1.44,1.23 and 1.64, respectively. More importantly, compared with AuNPs plus radiation, AgNPs plus radiation were significantly increased the levels of tumor cell apoptosis, cell death and autophagy. (3) In vivo:The same molar/mass concentration of AgNPs and AuNPs combined with radiation significantly prolonged the life span of glioma-bearing mice, and there was a significant difference in the survival time between the same molar/mass AgNPs and AuNPs nanoradiotherapy groups.Conclusion:Both AuNPs and AgNPs can exhibit good radiosensitizing ability. The combination of AgNPs and radiotherapy has significantly enhanced antiglioma effects, which may be due to its higher proapoptotic activity. Our results suggest the clinical potential of AgNPs as a highly effective radiosensitizer in improving the outcome of malignant glioma radiotherapy.