title: Exposure to metal oxide nanoparticles in physiological fluid induced synergistic biological effects in a keratinocyte model.
abstract: Nanoparticles (NPs) possess distinctive physicochemical properties that in addition to differentiating them from their bulk counterparts can induce negative cellular consequences. Standard in vitro systems have served as the primary model for NP safety evaluations, but suffer from a lack physiological relevance. One way to overcome this limitation and evaluate NP characteristics under more accurate conditions is through the use of artificial physiological fluids, which mimic the composition of in vivo environments. In this study, we identified that copper oxide (CuO) and titanium dioxide (TiO2) NPs displayed modified behavior when dispersed in artificial interstitial fluid (IF) versus traditional media, including extensive agglomeration and increased particle deposition. When keratinocyte cells underwent CuO NP exposure, synergistic stress and toxicity responses occurred within an IF environment, correlating with augmented particle deposition. However, following IF incubation alone or concurrently with TiO2NPs, which are not innately toxic, no combinatorial responses were identified. These results indicate that synergistic outcomes arise when toxic NPs undergo fluid-induced alterations to key physicochemical properties and behaviors. This study highlights the necessity of carrying out NP characterization and safety assessments in physiologically-representative environments; as altered behavior patterns have the potential to induce bioresponses not identified within traditional models.
authors.affiliation: Department of Chemical and Materials Engineering, University of Dayton, 300 College Park, Dayton, OH 45469, USA.
authors.forename: Deidre S
authors.initials: DS
authors.lastname: Cathe
authors.affiliation: Department of Chemical and Materials Engineering, University of Dayton, 300 College Park, Dayton, OH 45469, USA.
authors.forename: Jasmine N
authors.initials: JN
authors.lastname: Whitaker
authors.affiliation: Department of Chemical and Materials Engineering, University of Dayton, 300 College Park, Dayton, OH 45469, USA.
authors.forename: Emily K
authors.initials: EK
authors.lastname: Breitner
authors.affiliation: Department of Chemical and Materials Engineering, University of Dayton, 300 College Park, Dayton, OH 45469, USA. Electronic address: kcomfort1@udayton.edu.
authors.forename: Kristen K
authors.initials: KK
authors.lastname: Comfort
mesh_terms: D002460:Cell Line; D003300:Copper / Q000633:toxicity*; D045604:Extracellular Fluid / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D053768:Metal Nanoparticles / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000378:metabolism; D018570:Risk Assessment; D014025:Titanium / Q000633:toxicity*; D018675:Toxicity Tests
chemical_list: D017382:Reactive Oxygen Species; C009495:titanium dioxide; D003300:Copper; D014025:Titanium; C030973:cupric oxide
keywords: Copper oxide; Interstitial fluid; Nanotoxicity; Oxidative stress; Titanium dioxide