Department of Chemistry, University of Michigan , 930 North University Avenue, Ann Arbor, Michigan 48109, United States.
ACS Appl Mater Interfaces. 2017 Apr 19;9(15):13037-13048. doi: 10.1021/acsami.7b01112. Epub 2017 Apr 10.
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 (∼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.
金（Au）纳米材料的形状效应对癌症放射治疗的效率的影响尚未得到充分阐明。为了解决这个问题，我们合成了具有不同形状但平均尺寸相似（约 50nm）的 Au 纳米材料，包括球形金纳米颗粒（GNPs）、金纳米刺（GNSs）和金纳米棒（GNRs），并将其功能化与聚乙二醇（PEG）分子。尽管所有这些 Au 纳米结构都涂有相同的 PEG 分子，但它们的细胞摄取行为却有很大的不同。与孵育 24 小时后的 KB 癌细胞相比，GNPs 的细胞反应最高（基于相同的金质量）。细胞内摄取的顺序为 GNPs>GNSs>GNRs。我们的比较研究表明，所有这些 PEG 化的 Au 纳米结构在 X 射线照射下或多或少都能诱导增强癌细胞杀伤率。通过多靶点单击模型计算的增敏增强比（SER）分别为 1.62、1.37 和 1.21，对应于 GNPs、GNSs 和 GNRs 的处理，表明 GNPs 在 X 射线照射下比 GNSs 和 GNRs 具有更高的抗癌效率。通过将三种类型的 Au 纳米材料的 SER 除以它们相应的细胞摄取量，得到几乎相同的值，这表明 GNPs 的更高 SER 是由于其更高的细胞摄取效率。上述结果表明，辐射增强效应取决于内化的金原子数量。因此，为了在癌症放射治疗中实现强烈的放射增敏效果，有必要使用具有高细胞内化的基于 Au 的纳米材料。进一步研究放射增敏机制表明，Au 纳米结构诱导的 ROS 生成和细胞周期重分布在增强放射增敏中发挥了重要作用。综上所述，我们的结果表明，基于 Au 的纳米材料的形状对癌症放射治疗有显著影响。本工作可为基于 Au 的纳米结构在癌症放射治疗中的设计和应用提供重要指导。
