Enhancement of radiotherapy efficacy by silver nanoparticles in hypoxic glioma cells

Radiotherapy is one of the most widely used treatments for therapy of malignant tumors, but resistance to radiation of hypoxic cells in tumor tissues is still a serious concern. Previous studies have demonstrated that silver nanoparticles (AgNPs) enhance the radiosensitivity of human glioma cells in vitro, but the effect of AgNPs on hypoxic glioma cells has not been investigated in detail. The main purpose of this study is to evaluate the radiosensitizing efficacy of AgNPs on hypoxic glioma cells. The half maximal inhibitory concentration (IC50) values of AgNPs for the hypoxic U251 cells and C6 cells were 30.32 μg/mL and 27.53 μg/mL, respectively. The sensitization enhancement ratio (SER) demonstrated that AgNPs exhibit higher capacity in radiosensitization in hypoxic cells (U251: 1.78; C6: 1.84) than that in normoxic cells (U251: 1.34; C6: 1.45). The underlying mechanism of AgNPs' radiosensitization in hypoxic cells is through the promotion of apoptosis and enhanced destructive autophagy. There is evidence of crosstalk between apoptosis and autophagy in AgNPs-radiosensitized hypoxic cells where inhibition of autophagy results in decreased apoptosis. These findings suggest that AgNPs can be used as a highly effective nano-radiosensitizer for the treatment of hypoxic glioma.