title: Biomimicry 3D gastrointestinal spheroid platform for the assessment of toxicity and inflammatory effects of zinc oxide nanoparticles.
abstract: Our current mechanistic understanding on the effects of engineered nanoparticles (NPs) on cellular physiology is derived mainly from 2D cell culture studies. However, conventional monolayer cell culture may not accurately model the mass transfer gradient that is expected in 3D tissue physiology and thus may lead to artifactual experimental conclusions. Herein, using a micropatterned agarose hydrogel platform, the effects of ZnO NPs (25 nm) on 3D colon cell spheroids of well-defined sizes are examined. The findings show that cell dimensionality plays a critical role in governing the spatiotemporal cellular outcomes like inflammatory response and cytotoxicity in response to ZnO NPs treatment. More importantly, ZnO NPs can induce different modes of cell death in 2D and 3D cell culture systems. Interestingly, the outer few layers of cells in 3D model could only protect the inner core of cells for a limited time and periodically slough off from the spheroids surface. These findings suggest that toxicological conclusions made from 2D cell models might overestimate the toxicity of ZnO NPs. This 3D cell spheroid model can serve as a reproducible platform to better reflect the actual cell response to NPs and to study a more realistic mechanism of nanoparticle-induced toxicity.
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore, 117585, Singapore.
authors.forename: Sing Ling
authors.initials: SL
authors.lastname: Chia
authors.forename: Chor Yong
authors.initials: CY
authors.lastname: Tay
authors.forename: Magdiel I
authors.initials: MI
authors.lastname: Setyawati
authors.forename: David T
authors.initials: DT
authors.lastname: Leong
mesh_terms: D040761:Biomimetic Materials / Q000737:chemistry; D018929:Cell Culture Techniques / Q000295:instrumentation*; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced; D008422:Materials Testing; D053768:Metal Nanoparticles / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D018874:Spheroids, Cellular / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D013499:Surface Properties; D054457:Tissue Scaffolds / Q000737:chemistry; D014407:Tumor Cells, Cultured; D015034:Zinc Oxide / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D017382:Reactive Oxygen Species; D015034:Zinc Oxide
keywords: 3D cell cultures; inflammatory responses; nanotoxicity; oxidative stress; zinc oxide nanoparticles