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Decrease of Reactive Oxygen Species-Related Biomarkers in the Tissue-Mimic 3D Spheroid Culture of Human Lung Cells Exposed to Zinc Oxide Nanoparticles

Title
Decrease of Reactive Oxygen Species-Related Biomarkers in the Tissue-Mimic 3D Spheroid Culture of Human Lung Cells Exposed to Zinc Oxide Nanoparticles
Author(s)
Kim, Eun JooJeon, Won BaeKim, SoonhyunLee, Soo Keun
DGIST Authors
Kim, Eun JooJeon, Won BaeKim, SoonhyunLee, Soo Keun
Issued Date
2014-05
Type
Article
Article Type
Article
Author Keywords
NanotoxicityZinc Oxide Nanoparticle3D Spheroid CultureElastin-Like ProteinOxidative Stress
Keywords
ELASTIN-LIKE POLYPEPTIDEIN-VITRO TOXICITYOXIDATIVE STRESSCANCER-CELLSSILVER NANOPARTICLESHUMAN HEPATOCYTEAPOPTOSISCYTOTOXICITYPROTEINSMITOCHONDRIA
ISSN
1533-4880
Abstract
Common 2-dimensional (2D) cell cultures do not adequately represent cell-cell and cell-matrix signaling and substantially different diffusion/transport pathways. To obtain tissue-mimic information on nanoparticle toxicity from in vitro cell tests, we used a 3-dimensional (3D) culture of human lung cells (A549) prepared with elastin-like peptides modified with an arginine-glycine-aspartate motif. The 3D cells showed different cellular phenotypes, gene expression profiles, and functionalities compared to the 2D cultured cells. In gene array analysis, 3D cells displayed the induced extracellular matrix (ECM)-related biological functions such as cell-to-cell signaling and interaction, cellular function and maintenance, connective tissue development and function, molecular transport, and tissue morphology. Additionally, the expression of ECM-related molecules, such as laminin, fibronectin, and insulin-like growth factor binding protein 3 (IGFBP3), was simultaneously induced at both mRNA and protein levels. When 0.08-50 μg/ml zinc oxide nanoparticles (ZnO-NPs) were administered to 2D and 3D cells, the cell proliferation was not significantly changed. The level of molecular markers for oxidative stress, such as superoxide dismutase (SOD), Bcl-2, ATP synthase, and Complex IV (cytochrome C oxidase), was significantly reduced in 2D culture when exposed to 10 μg/ml ZnO-NPs, but no significant decrease was detected in 3D culture when exposed to the same concentration of ZnO-NPs. In conclusion, the tissue-mimic phenotype and functionality of 3D cells could be achieved through the elevated expression of ECM components. The 3D cells were expected to help to better predict the nanotoxicity of ZnO-NPs at tissue-level by increased cell-cell and cell-ECM adhesion and signaling. The tissue-mimic morphology would also be useful to simulate the diffusion/transport of the nanoparticles in vitro. Copyright © 2014 American Scientific Publishers.
URI
http://hdl.handle.net/20.500.11750/5257
DOI
10.1166/jnn.2014.8257
Publisher
American Scientific Publishers
Related Researcher
  • 김은주 Kim, Eunjoo 전자정보시스템연구부
  • Research Interests Biomarker; liquid biopsy; molecular diagnosis; nanobiosensor; drug delivery; exosome
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Appears in Collections:
Division of Energy Technology 1. Journal Articles
Division of Biotechnology 1. Journal Articles
Division of Electronics & Information System 1. Journal Articles

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