a Department of Nuclear Science and Engineering , Nanjing University of Aeronautics and Astronautics , Nanjing P.R. China.
b Jiangsu Key Laboratory for Biomaterials and Devices , Southeast University , Nanjing , P.R. China.
Artif Cells Nanomed Biotechnol. 2018;46(sup3):S922-S930. doi: 10.1080/21691401.2018.1518912. Epub 2018 Oct 11.
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.
放射疗法是治疗恶性肿瘤最广泛使用的治疗方法之一，但肿瘤组织中缺氧细胞对辐射的抵抗仍然是一个严重的问题。先前的研究表明，银纳米粒子（AgNPs）可增强体外人神经胶质瘤细胞的放射敏感性，但 AgNPs 对缺氧神经胶质瘤细胞的影响尚未详细研究。本研究的主要目的是评估 AgNPs 对缺氧神经胶质瘤细胞的放射增敏作用。AgNPs 对缺氧 U251 细胞和 C6 细胞的半最大抑制浓度（IC50）值分别为 30.32μg/mL 和 27.53μg/mL。增敏增强比（SER）表明，AgNPs 在缺氧细胞（U251：1.78；C6：1.84）中比在常氧细胞（U251：1.34；C6：1.45）中具有更高的放射增敏能力。AgNPs 促进缺氧细胞凋亡和增强破坏性自噬是其放射增敏的潜在机制。在 AgNPs 放射增敏的缺氧细胞中，凋亡和自噬之间存在串扰，自噬的抑制导致凋亡减少。这些发现表明，AgNPs 可作为治疗缺氧神经胶质瘤的高效纳米放射增敏剂。
