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金纳米粒子的合成及其对接受兆伏 X 射线照射的乳腺癌细胞细胞周期的影响。

Syntheses of gold nanoparticles and their impact on the cell cycle in breast cancer cells subjected to megavoltage X-ray irradiation.

机构信息

Laboratory for Protein Dynamics, Ruđer Bošković Institute, 10002 Zagreb, Croatia.

University Hospital Center Zagreb, Kišpatićeva 12, 10000 Zagreb, Croatia.

出版信息

Mater Sci Eng C Mater Biol Appl. 2018 Oct 1;91:486-495. doi: 10.1016/j.msec.2018.05.066. Epub 2018 May 22.

Abstract

Gold nanoparticles (AuNPs) were synthesized in the presence of citrate (Au-CIT), glutathione (Au-GSH) and aminodextran (Au-DEX) in order to modify AuNPs surfaces and to increase their cellular uptake in the breast cancer cells MDA-MB-231. AuNPs were characterized with respect to their particle size, shape and colloidal stability in an aqueous solution and cell media. The mass accumulation of each AuNP type inside cancer cells was determined quantitatively, using Inductive Coupled Plasma - mass spectroscopy. The sub-cellular accumulation was studied using Transmission Electron Microscopy (TEM). It was found that gold nanoparticles applied to cancer cells were localized in cytoplasmic vesicles and that the highest uptake was shown in the presence of Au-GSH nanoparticles. The effect of AuNPs on the cell cycle was investigated using flow cytometry and Western blot analysis. The gold nanoparticles alone did not affect the cell cycle, as shown by flow cytometry. Furthermore, the cancer cells were irradiated using conventional clinically relevant high-energy X-ray radiation of 6 MV in the dose of 4 Gy. The results on cells only irradiated showed an S phase arrest six and 8 h after irradiation, and a G2/M arrest 24 and 48 h after irradiation. The irradiation of breast cancer cells treated with AuNPs has shown no significant variation in cell cycle distribution as opposed to X-ray radiation alone.

摘要

为了修饰金纳米粒子(AuNPs)的表面并提高其在乳腺癌 MDA-MB-231 细胞中的细胞摄取率,在柠檬酸(Au-CIT)、谷胱甘肽(Au-GSH)和氨基葡聚糖(Au-DEX)的存在下合成了金纳米粒子。AuNPs 的粒径、形状和胶体稳定性在水溶液和细胞培养基中进行了表征。使用电感耦合等离子体质谱法(ICP-MS)定量测定了每种 AuNP 类型在癌细胞内的质量积累。使用透射电子显微镜(TEM)研究了亚细胞积累。结果发现,应用于癌细胞的金纳米粒子定位于细胞质囊泡中,并且在 Au-GSH 纳米粒子存在下显示出最高的摄取率。使用流式细胞术和 Western blot 分析研究了 AuNPs 对细胞周期的影响。如流式细胞术所示,单独的金纳米粒子对细胞周期没有影响。此外,使用 6 MV 的常规临床相关高能 X 射线在 4 Gy 的剂量下对癌细胞进行照射。仅照射细胞的结果显示,照射后 6 和 8 小时 S 期停滞,照射后 24 和 48 小时 G2/M 期停滞。与单独的 X 射线辐射相比,用 AuNPs 处理的乳腺癌细胞的照射显示细胞周期分布没有明显变化。

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