Shape-Dependent Radiosensitization Effect of Gold Nanostructures in Cancer Radiotherapy: Comparison of Gold Nanoparticles, Nanospikes, and Nanorods
Shape-Dependent Radiosensitization Effect of Gold Nanostructures in Cancer Radiotherapy: Comparison of Gold Nanoparticles, Nanospikes, and Nanorods
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金纳米结构在癌症放射治疗中的形状依赖性放射增敏作用：金纳米颗粒、纳米尖峰和纳米棒的比较
DOI：
10.1021/acsami.7b01112
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发表时间：
2017-04-19
影响因子：
9.5
通讯作者：
Chen, Zhan
中科院分区：
文献类型：
--
作者：
Ma, Ningning;Wu, Fu-Gen;Chen, Zhan
金（Au）纳米材料的形状对癌症放射治疗效率的影响尚未完全阐明。为了解决这一问题，合成了具有不同形状但相似平均尺寸（类似于50 nm）的Au纳米材料，包括球形金纳米颗粒（GNP）、金纳米钉（GNS）和金纳米棒（GNR），并用聚（乙二醇）（PEG）分子官能化。尽管所有这些Au纳米结构都涂覆有相同的PEG分子，但它们的细胞摄取行为显著不同。在与KB癌细胞孵育24小时后，与GNS和GNR（基于相同的金质量）相比，GNP显示出最高的细胞应答。细胞摄取的顺序为GNPs > GNSs > GNRs。我们的比较研究表明，所有这些聚乙二醇化的Au纳米结构可以诱导增强的癌细胞杀伤率或多或少的X射线照射。通过多靶点单次击中模型计算的增敏增强比（Sers）分别为1.62、1.37和1.21，分别对应于GNP、GNS和GNRs的处理，表明GNP在X射线照射后显示出比GNS和GNRs更高的抗癌效率。通过将三种类型的Au纳米材料的Sers除以其相应的细胞摄取量获得几乎相同的值，表明GNP的较高SER是由于其高得多的细胞摄取效率。上述结果表明，辐射增强效应取决于内化的金原子的量。因此，要在癌症放射治疗中实现较强的放射增敏作用，必须使用具有高细胞内化的Au基纳米材料。放射增敏机制的进一步研究表明，Au纳米结构诱导的ROS生成和细胞周期重新分布在增强放射增敏中起重要作用。综上所述，我们的研究结果表明，Au基纳米材料的形状对癌症放射治疗有显着影响。本工作为Au纳米结构的设计和在肿瘤放疗中的应用提供了重要指导。
The shape effect of gold (Au) nanomaterials on the efficiency of cancer radiotherapy has not been fully elucidated. To address this issue, Au nanomaterials with different shapes but similar average size (similar to 50 nm) including spherical gold nanoparticles (GNPs), gold nanospikes (GNSs), and gold nanorods (GNRs) were synthesized and functionalized with poly(ethylene glycol) (PEG) molecules. Although all of these Au nanostructures were coated with the same PEG molecules, their cellular uptake behavior differed significantly. The GNPs showed the highest cellular responses as compared to the GNSs and the GNRs (based on the same gold mass) after incubation with KB cancer cells for 24 h. The cellular uptake in cells increased in the order of GNPs > GNSs > GNRs. Our comparative studies indicated that all of these PEGylated Au nanostructures could induce enhanced cancer cell killing rates more or less upon X-ray irradiation. The sensitization enhancement ratios (SERs) calculated by a multitarget single hit model were 1.62, 1.37, and 1.21 corresponding to the treatments of GNPs, GNSs, and GNRs, respectively, demonstrating that the GNPs showed a higher anticancer efficiency than both GNSs and GNRs upon X-ray irradiation. Almost the same values were obtained by dividing the SERs of the three types of Au nanomaterials by their corresponding cellular uptake amounts, indicating that the higher SER of GNPs was due to their much higher cellular uptake efficiency. The above results indicated that the radiation enhancement effects were determined by the amount of the internalized gold atoms. Therefore, to achieve a strong radiosensitization effect in cancer radiotherapy, it is necessary to use Au-based nanomaterials with a high cellular internalization. Further studies on the radiosensitization mechanisms demonstrated that ROS generation and cell cycle redistribution induced by Au nanostructures played essential roles in enhancing radiosensitization. Taken together, our results indicated that the shape of Au-based nanomaterials had a significant influence on cancer radiotherapy. The present work may provide important guidance for the design and use of Au nanostructures in cancer radiotherapy.