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使用基于阻抗的实时细胞分析仪评估镓基和铟基纳米颗粒对人支气管上皮细胞的细胞毒性

Cytotoxicity Assessment of Gallium- and Indium-Based Nanoparticles Toward Human Bronchial Epithelial Cells Using an Impedance-Based Real-Time Cell Analyzer.

作者信息

Nguyen Chi H, Zeng Chao, Boitano Scott, Field Jim A, Sierra-Alvarez Reyes

机构信息

Department of Chemical and Environmental Engineering, University of Arizona, Tucson, AZ, USA.

Department of Physiology and The Asthma and Airway Disease Research Center, University of Arizona, Tucson, AZ, USA.

出版信息

Int J Toxicol. 2020 May/Jun;39(3):218-231. doi: 10.1177/1091581820914255. Epub 2020 Mar 31.

DOI:10.1177/1091581820914255
PMID:32228215
Abstract

The semiconductor manufacturing sector plans to introduce III/V film structures (eg, gallium arsenide (GaAs), indium arsenide (InAs) onto silicon wafers due to their high electron mobility and low power consumption. Aqueous solutions generated during chemical and mechanical planarization of silicon wafers can contain a mixture of metal oxide nanoparticles (NPs) and soluble indium, gallium, and arsenic. In this work, the cytotoxicity induced by Ga- and In-based NPs (GaAs, InAs, GaO, InO) and soluble III-V salts on human bronchial epithelial cells (16HBE14o-) was evaluated using a cell impedance real-time cell analysis (RTCA) system. The RTCA system provided inhibition data at different concentrations for multiple time points, for example, GaAs (25 mg/L) caused 60% inhibition after 8 hours of exposure and 100% growth inhibition after 24 hours. Direct testing of As(III) and As(V) demonstrated significant cytotoxicity with 50% growth inhibition concentrations after 16-hour exposure (IC) of 2.4 and 4.5 mg/L, respectively. Cell signaling with rapid rise and decrease in signal was unique to arsenic cytotoxicity, a precursor of strong cytotoxicity over the longer term. In contrast with arsenic, soluble gallium(III) and indium(III) were less toxic. Whereas the oxide NPs caused low cytotoxicity, the arsenide compounds were highly inhibitory (IC of GaAs and InAs = 6.2 and 68 mg/L, respectively). Dissolution experiments over 7 days revealed that arsenic was fully leached from GaAs NPs, whereas only 10% of the arsenic was leached out of InAs NPs. These results indicate that the cytotoxicity of GaAs and InAs NPs is largely due to the dissolution of toxic arsenic species.

摘要

半导体制造行业计划将III/V族薄膜结构(如砷化镓(GaAs)、砷化铟(InAs))引入硅片,因为它们具有高电子迁移率和低功耗。硅片化学机械平面化过程中产生的水溶液可能含有金属氧化物纳米颗粒(NPs)以及可溶性铟、镓和砷的混合物。在本研究中,使用细胞阻抗实时细胞分析(RTCA)系统评估了基于镓和铟的纳米颗粒(GaAs、InAs、GaO、InO)以及可溶性III/V族盐对人支气管上皮细胞(16HBE14o-)的细胞毒性。RTCA系统提供了多个时间点不同浓度下的抑制数据,例如,GaAs(25 mg/L)在暴露8小时后导致60%的抑制率,24小时后生长抑制率达到100%。对As(III)和As(V)的直接测试表明,它们具有显著的细胞毒性,暴露16小时后的50%生长抑制浓度(IC)分别为2.4和4.5 mg/L。信号快速上升和下降的细胞信号传导是砷细胞毒性所特有的,从长期来看,这是强细胞毒性的先兆。与砷相比,可溶性镓(III)和铟(III)的毒性较小。氧化物纳米颗粒引起的细胞毒性较低,而砷化物化合物具有高度抑制性(GaAs和InAs的IC分别为6.2和68 mg/L)。为期7天的溶解实验表明,砷从GaAs纳米颗粒中完全浸出,而InAs纳米颗粒中仅浸出10%的砷。这些结果表明,GaAs和InAs纳米颗粒的细胞毒性很大程度上归因于有毒砷物种的溶解。

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