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ZnO/CNT@FeO 诱导慢性髓性白血病 (CML) 细胞产生 ROS 介导的细胞凋亡:纳米颗粒在白血病治疗中的新前景。

ZnO/CNT@FeO induces ROS-mediated apoptosis in chronic myeloid leukemia (CML) cells: an emerging prospective for nanoparticles in leukemia treatment.

机构信息

Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

School of Chemical Engineering, College of Engineering, Institute of Petroleum Engineering, University of Tehran, Tehran, Iran.

出版信息

Artif Cells Nanomed Biotechnol. 2020 Dec;48(1):735-745. doi: 10.1080/21691401.2020.1748885.

Abstract

The advent of nanoparticles revolutionised the drug delivery systems in human diseases; however, their prominent role was highlighted in the cancer-based therapies, where this technology could specifically target cancer cells. Herein, we decided to combine two nanoparticles FeO and ZnO to fabricate a new anti-cancer nanocomposite. Noteworthy, hydroxylated carbon nanotube (CNT) was used to increase the water-solubility of the compound, improving its uptake by malignant cells. This study was designed to evaluate the anticancer property as well as the molecular mechanisms of ZnO/CNT@FeO nanocomposite cytotoxicity in CML-derived K562 cells. Our results outlined that ZnO/CNT@FeO decreased the proliferative capacity of K562 cells through induction of G1 arrest and induced apoptosis probably via ROS-dependent upregulation of FOXO3a and SIRT1. The results of qRT-PCR analysis also demonstrated that while ZnO/CNT@FeO significantly increased the expression of pro-apoptotic genes in K562 cells, it had no significant inhibitory effect on the expression levels of anti-apoptotic target genes of NF-κB; proposing an attenuating role of NF-κB signalling pathway in K562 cell response to ZnO/CNT@FeO. Synergistic experiment showed that ZnO/CNT@FeO could enhance the cytotoxic effects of imatinib on K562 cells. Overall, it seems that pharmaceutical application of nanocomposites possesses novel promising potential for leukaemia treatment strategies.

摘要

纳米粒子的出现彻底改变了人类疾病的药物输送系统;然而,它们在癌症治疗中的突出作用得到了强调,因为这项技术可以专门针对癌细胞。在这里,我们决定将两种纳米粒子 FeO 和 ZnO 结合起来制造一种新型抗癌纳米复合材料。值得注意的是,羟基化碳纳米管 (CNT) 被用于提高化合物的水溶性,从而提高其被恶性细胞吸收的能力。本研究旨在评估 ZnO/CNT@FeO 纳米复合材料在 CML 衍生的 K562 细胞中的抗癌特性和细胞毒性的分子机制。我们的结果表明,ZnO/CNT@FeO 通过诱导 G1 期阻滞降低 K562 细胞的增殖能力,并通过 ROS 依赖性上调 FOXO3a 和 SIRT1 诱导细胞凋亡。qRT-PCR 分析的结果还表明,虽然 ZnO/CNT@FeO 显著增加了 K562 细胞中促凋亡基因的表达,但对 NF-κB 的抗凋亡靶基因的表达水平没有显著抑制作用;提出 NF-κB 信号通路在 K562 细胞对 ZnO/CNT@FeO 的反应中具有减弱作用。协同实验表明,ZnO/CNT@FeO 可以增强 imatinib 对 K562 细胞的细胞毒性作用。总的来说,似乎纳米复合材料的药物应用为白血病治疗策略提供了新的有希望的潜力。

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