title: Evaluation of the cytotoxic and inflammatory potential of differentially shaped zinc oxide nanoparticles.
abstract: Zinc oxide (ZnO) nanoparticles have wide-ranging applications in a diverse array of industrial and consumer products, from ceramic manufacture and paint formulation to sunscreens and haircare products. Hence, it is imperative to rigorously characterize the health and safety aspects of human exposure to ZnO nanoparticles. This study therefore evaluated the cellular association, cytotoxic and inflammatory potential of spherical and sheet-shaped ZnO nanoparticles (of approximately the same specific surface area ≈30 cm²/g) on mouse and human cell lines (RAW-264.7 and BEAS-2B respectively), as well as with primary cultures of mouse bone marrow-derived dendritic cells (DC). The WST-8 assay demonstrated dose-dependent effects on the cytotoxicity of spherical and sheet-shaped ZnO nanoparticles on both RAW-264.7 and BEAS-2B cells, even though there was no significant effect of shape on the cytotoxicity of ZnO nanoparticles. There was however higher cellular association of spherical versus sheet-shaped ZnO nanoparticles. Measurement of reactive oxygen species (ROS) with the 2',7'-dichlorfluorescein-diacetate (DCFH-DA) assay indicated up to 4-folds increase in ROS level upon exposure to ZnO nanoparticles, but there was again no significant difference between both ZnO nanoparticle shapes. Exposure of primary dendritic cells to ZnO nanoparticles upregulated expression of CD80 and CD86 (well-known markers of DC activation and maturation) and stimulated release of pro-inflammatory cytokines--IL-6 and TNF-α, thus pointing to the potential of ZnO nanoparticles in inducing inflammation. Hence, our study indicated that ZnO nanoparticles can have potential detrimental effects on cells even at dosages where there are little or no observable cytotoxic effects.
authors.affiliation: School of Materials Science and Engineering, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
authors.forename: Boon Chin
authors.initials: BC
authors.lastname: Heng
authors.forename: Xinxin
authors.initials: X
authors.lastname: Zhao
authors.forename: Eng Chok
authors.initials: EC
authors.lastname: Tan
authors.forename: Nurulain
authors.initials: N
authors.lastname: Khamis
authors.forename: Aarti
authors.initials: A
authors.lastname: Assodani
authors.forename: Sijing
authors.initials: S
authors.lastname: Xiong
authors.forename: Christiane
authors.initials: C
authors.lastname: Ruedl
authors.forename: Kee Woei
authors.initials: KW
authors.lastname: Ng
authors.forename: Joachim Say-Chye
authors.initials: JS
authors.lastname: Loo
mesh_terms: D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018675:Toxicity Tests; D015034:Zinc Oxide / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D017382:Reactive Oxygen Species; D015034:Zinc Oxide