Quantitative analyses of amount and localization of radiosensitizer gold nanoparticles interacting with cancer cells to optimize radiation therapy
Quantitative analyses of amount and localization of radiosensitizer gold nanoparticles interacting with cancer cells to optimize radiation therapy
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DOI：
10.1016/j.bbrc.2018.12.016
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发表时间：
2019-01-22
影响因子：
3.1
通讯作者：
Gonda, Kohsuke
中科院分区：
文献类型：
--
作者：
Hatoyama, Keiichiro;Kitamura, Narufumi;Gonda, Kohsuke
先前的研究表明，金纳米粒子（AuNPs）是有用的放射增敏剂，其在低剂量辐射下优化放射治疗。然而，AuNP放射增敏的机制，包括与癌细胞相互作用的AuNP的量和定位，尚未被量化。为了回答这些问题，我们制备了通过聚乙二醇（PEG）链与抗人表皮生长因子受体2型（HER 2）抗体缀合的金纳米颗粒（AuNP-PEG-HER 2ab）。AuNP-PEG-HER 2ab特异性结合表达HER 2的癌细胞并通过内吞作用进入细胞。AuNP-PEG-HER 2ab是否发生内吞作用对AuNP-PEG-HER 2ab体外放射增敏效果没有影响。体外放射增敏效果与AuNP-PEG-HER 2ab剂量或X射线剂量有关。此外，给予荷瘤小鼠的AuNP-PEG-HER 2ab定位于肿瘤组织的外周和肿瘤深部组织中癌细胞的细胞核附近。AuNP-PEG-HER 2ab在肿瘤组织中的定位是体内强大放射增敏功效的重要因素。(C)2018爱思唯尔公司All rights reserved.
Previous studies showed that gold nanoparticles (AuNPs) are useful radiosensitizers which optimize radiation therapy under low-dose radiation. However, the mechanisms of AuNP radiosensitization, including the amount and localization of the AuNPs interacting with cancer cells, has not yet been quantified. To answer these questions, we prepared AuNPs conjugated with anti-human epidermal growth factor receptor type 2 (HER2) antibody via polyethylene glycol (PEG) chains (AuNP-PEG-HER2ab). AuNP-PEG-HER2ab specifically bound to the HER2-expressing cancer cells and entered the cells via endocytosis. Whether endocytosis of AuNP-PEG-HER2ab occurred had no effect on radiosensitization efficacy by AuNP-PEG-HER2ab in vitro. The radiosensitization efficacy in vitro depended on dose of AuNP-PEG-HER2ab or dose of X-ray. Moreover, AuNP-PEG-HER2ab administrated into tumor-bearing mice was localized to both the periphery of the tumor tissue and near the nuclei in cancer cells in tumor deep tissue. The localization of AuNP-PEG-HER2ab in tumor tissues was important factors for in vivo powerful radiosensitization efficacy. (C) 2018 Elsevier Inc. All rights reserved.