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氧化锌纳米结构的制备和生长机制及其对人脑瘤 U87、宫颈癌 HeLa 和正常 HEK 细胞的细胞毒性作用。

Fabrication and growth mechanism of ZnO nanostructures and their cytotoxic effect on human brain tumor U87, cervical cancer HeLa, and normal HEK cells.

机构信息

Energy Materials and Surface Science Laboratory, Solar Energy Research Center, School of Chemical Engineering, Chonbuk National University, Jeonju, 561-756, South Korea.

出版信息

J Biol Inorg Chem. 2011 Mar;16(3):431-42. doi: 10.1007/s00775-010-0740-0. Epub 2010 Dec 8.

Abstract

ZnO nanostructures of diverse shape were grown via a solution process with different precursors and conditions. Morphological investigation of the nanostructures was carried out using field emission scanning electron microscopy and transmission microscopy observations and revealed that the nanostructures exhibit a wurtzite phase with an ideal lattice fringe distance of approximately 0.52 nm. The powder crystallinity was examined via X-ray diffraction spectroscopy. Screening results from anticancer studies of the effects on human brain tumor U87, cervical cancer HeLa, and normal HEK cells of ZnO nanostructures of diverse shape were obtained and indicate promising activity that varies with changes in the structure and the size of the particles. Treatment-induced cell death [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and survival assay], growth inhibition, cytogenetic damage (formation of micronuclei), and apoptosis were studied as parameters for the cellular response. Treatment with nanostructures enhanced growth inhibition and cell death in a concentration-dependent manner in both U87 and HeLa cell lines. At higher concentrations (above 15.6 μg/ml) the cytotoxic effects of the nanoparticles were highly synergistic and mainly mediated through apoptosis, implying the possible interactions of lesions caused by the agents. The enhanced cell death due to nanoparticles was accompanied by a significant increase (2-3 fold at 31.25 μg/ml) in the formation of micronuclei in U87 cells. The increase in the formation of micronuclei observed after treatment indicates that these structures may interfere with the rejoining of DNA strand breaks. Among all the nanostructures, nanoparticles and sheets exhibited potent activity against both HeLa and U87 cells. However, despite potent in vitro activity, all nanostructures exhibited diminished cytotoxicity against normal human HEK cells at all effective concentrations.

摘要

采用不同的前体和条件通过溶液法生长了具有不同形状的 ZnO 纳米结构。通过场发射扫描电子显微镜和透射显微镜观察对纳米结构的形貌进行了研究,结果表明纳米结构具有纤锌矿相,理想的晶格条纹间距约为 0.52nm。通过 X 射线衍射光谱法检查了粉末结晶度。获得了不同形状 ZnO 纳米结构对人脑肿瘤 U87、宫颈癌 HeLa 和正常 HEK 细胞的抗癌作用的筛选结果,表明其活性具有很大的潜力,并且随结构和颗粒尺寸的变化而变化。研究了诱导细胞死亡(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐和生存测定)、生长抑制、细胞遗传学损伤(形成微核)和细胞凋亡作为细胞反应的参数。在 U87 和 HeLa 细胞系中,纳米结构以浓度依赖的方式增强了生长抑制和细胞死亡。在更高的浓度(高于 15.6μg/ml)下,纳米颗粒的细胞毒性作用具有高度协同作用,主要通过细胞凋亡介导,这意味着可能与药物引起的损伤相互作用。由于纳米颗粒导致的细胞死亡增加伴随着 U87 细胞中微核形成的显著增加(31.25μg/ml 时增加 2-3 倍)。处理后观察到微核形成增加表明这些结构可能干扰 DNA 链断裂的重新连接。在所有纳米结构中,纳米颗粒和薄片对 HeLa 和 U87 细胞均表现出很强的活性。然而,尽管在体外具有很强的活性,但所有纳米结构在所有有效浓度下对正常人类 HEK 细胞的细胞毒性均降低。

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