Ultrathin gold nanowires to enhance radiation therapy
Ultrathin gold nanowires to enhance radiation therapy
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超细金纳米线增强放射治疗
DOI：
10.1186/s12951-020-00678-3
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发表时间：
2020-09-11
影响因子：
10.2
通讯作者：
Ma, Qingjie
中科院分区：
文献类型：
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作者：
Bai, Lin;Jiang, Fangchao;Ma, Qingjie
背景放射治疗是癌症的主要治疗选择。由于正常的组织毒性，放射增敏剂通常用于提高RT。特别是，重金属或高Z材料，如金纳米颗粒，已作为辐射增敏剂进行了研究。然而，到目前为止，相关的研究主要集中在球形金纳米颗粒上。本研究首次对超细金纳米线作为辐射增敏剂的潜力进行了评价。然后在合成的金纳米线上涂上一层聚乙二醇化的磷脂，使其可溶于水。作为对比，还合成了包覆相同磷脂的球形金纳米颗粒。金纳米线和金纳米球首先在溶液中进行了测试，以确定它们在辐射下增强自由基产生的能力。然后将它们与4T1细胞孵育，以评估它们是否可以在辐射下提高细胞的氧化应激。最后，将金纳米线和金纳米颗粒注射到4T1异种移植瘤模型中，然后对肿瘤进行照射(3Gyd/d，连续三天)。结果我们的研究表明，在X射线照射下，金纳米线在促进自由基产生方面优于金纳米球。体外分析发现，金纳米线的存在导致辐射下脂质过氧化和细胞内氧化应激的增加。在体内测试时，金纳米线加辐射导致的肿瘤抑制效果好于金纳米球加辐射。此外，在谷胱甘肽的作用下，金纳米线逐渐还原为较短的纳米线，这可能有利于分次放射治疗。结论金纳米线是一种很有前途的放射增敏剂，可以安全地注射到肿瘤中以加强放射治疗。虽然目前的研究是在乳腺癌模型中进行的，但该方法可以扩展到其他类型的癌症的治疗。
Background Radiation therapy is a main treatment option for cancer. Due to normal tissue toxicity, radiosensitizers are commonly used to enhance RT. In particular, heavy metal or high-Z materials, such as gold nanoparticles, have been investigated as radiosensitizers. So far, however, the related studies have been focused on spherical gold nanoparticles. In this study, we assessed the potential of ultra-thin gold nanowires as a radiosensitizer, which is the first time.Methods Gold nanowires were synthesized by the reduction of HAuCl(4)in hexane. The as-synthesized gold nanowires were then coated with a layer of PEGylated phospholipid to be rendered soluble in water. Spherical gold nanoparticles coated with the same phospholipid were also synthesized as a comparison. Gold nanowires and gold nanospheres were first tested in solutions for their ability to enhance radical production under irradiation. They were then incubated with 4T1 cells to assess whether they could elevate cell oxidative stress under irradiation. Lastly, gold nanowires and gold nanoparticles were intratumorally injected into a 4T1 xenograft model, followed by irradiation applied to tumors (3 Gy/per day for three days). Tumor growth was monitored and compared.Results Our studies showed that gold nanowires are superior to gold nanospheres in enhancing radical production under X-ray radiation. In vitro analysis found that the presence of gold nanowires caused elevated lipid peroxidation and intracellular oxidative stress under radiation. When tested in vivo, gold nanowires plus irradiation led to better tumor suppression than gold nanospheres plus radiation. Moreover, gold nanowires were found to be gradually reduced to shorter nanowires by glutathione, which may benefit fractionated radiation.Conclusion Our studies suggest that gold nanowires are a promising type of radiosensitizer that can be safely injected into tumors to enhance radiotherapy. While the current study was conducted in a breast cancer model, the approach can be extended to the treatment of other cancer types.