Abstract
Due to the widespread use of indium tin oxide (ITO), it is important to investigate its effect on human health. In this study, we evaluated the cellular effects of ITO nanoparticles (NPs), indium chloride (InCl3) and tin chloride (SnCl3) using human lung epithelial A549 cells. Transmission electron microscopy and inductively coupled plasma mass spectrometry were employed to study cellular ITO NP uptake. Interestingly, greater uptake of ITO NPs was observed, as compared with soluble salts. ITO NP species released could be divided into two types: 'indium release ITO' or 'tin release ITO'. We incubated A549 cells with indium release ITO, tin release ITO, InCl3 or SnCl2 and investigated oxidative stress, proinflammatory response, cytotoxicity and DNA damage. We found that intracellular reactive oxygen species were increased in cells incubated with indium release ITO, but not tin release ITO, InCl3 or SnCl2. Messenger RNA and protein levels of the inflammatory marker, interleukin-8, also increased following exposure to indium release ITO. Furthermore, the alkaline comet assay revealed that intracellular accumulation of indium ions induced DNA damage. Our results demonstrate that the accumulation of ionic indium, but not ionic tin, from ITO NPs in the intracellular matrix has extensive cellular effects.
Highlights
IntroductionSeveral studies have focused on clinical applications of NPs, including nanomedicine and drug-delivery systems [2, 3]
When indium tin oxide (ITO) NPs were dispersed in Dulbecco’s modified Eagle’s medium (DMEM)-fetal bovine serum (FBS), ITO NPs formed large secondary particles and sedimented within a few minutes by gravity
We found that when the ITO NPs were solubilized within the A549 cells, the metal ions released from Sample A were primarily tin ions, whereas those released from Sample B were indium ions
Summary
Several studies have focused on clinical applications of NPs, including nanomedicine and drug-delivery systems [2, 3] Despite these potential advantages, NPs induce several biological effects. ZnO, NiO and chromium oxide NPs solubilized in cell culture medium release the corresponding metal ions into the extracellular environment, exerting remarkable cytotoxicity [7, 10, 11]. We demonstrated that the ITO NPs possess the potential for inducing oxidative stress and DNA damage in the A549 cells [28]; possible differences in cellular effects between ITO NPs and their corresponding metal ionic species have not been assessed yet. We focused on the importance of ITO NP cellular uptake and the subsequent release of metal ions inside the cell.
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