title: Cell type-dependent changes in CdSe/ZnS quantum dot uptake and toxic endpoints.
abstract: Toxicity of nanoparticles (NPs) is often correlated with the physicochemical characteristics of the materials. However, some discrepancies are noted in in-vitro studies on quantum dots (QDs) with similar physicochemical properties. This is partly related to variations in cell type. In this study, we show that epithelial (BEAS-2B), fibroblast (HFF-1), and lymphoblastoid (TK6) cells show different biological responses following exposure to QDs. These cells represented the 3 main portals of NP exposure: bronchial, skin, and circulatory. The uptake and toxicity of negatively and positively charged CdSe:ZnS QDs of the same core size but with different surface chemistries (carboxyl or amine polymer coatings) were investigated in full and reduced serum containing media following 1 and 3 cell cycles. Following thorough physicochemical characterization, cellular uptake, cytotoxicity, and gross chromosomal damage were measured. Cellular damage mechanisms in the form of reactive oxygen species and the expression of inflammatory cytokines IL-8 and TNF-α were assessed. QDs uptake and toxicity significantly varied in the different cell lines. BEAS-2B cells demonstrated the highest level of QDs uptake yet displayed a strong resilience with minimal genotoxicity following exposure to these NPs. In contrast, HFF-1 and TK6 cells were more susceptible to toxicity and genotoxicity, respectively, as a result of exposure to QDs. Thus, this study demonstrates that in addition to nanomaterial physicochemical characterization, a clear understanding of cell type-dependent variation in uptake coupled to the inherently different capacities of the cell types to cope with exposure to these exogenous materials are all required to predict genotoxicity.
authors.affiliation: *Institute of Life Science, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK, Department of Medicine, Biomedical NMR Unit-MoSAIC, KU Leuven, B-3000 Leuven, Belgium and Institute for Materials Research, SCaPE, University of Leeds, Leeds LS2 9JT, UK *Institute of Life Science, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK, Department of Medicine, Biomedical NMR Unit-MoSAIC, KU Leuven, B-3000 Leuven, Belgium and Institute for Materials Research, SCaPE, University of Leeds, Leeds LS2 9JT, UK s.h.doak@swansea.ac.uk.
authors.forename: Bella B
authors.initials: BB
authors.lastname: Manshian
authors.affiliation: *Institute of Life Science, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK, Department of Medicine, Biomedical NMR Unit-MoSAIC, KU Leuven, B-3000 Leuven, Belgium and Institute for Materials Research, SCaPE, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Stefaan J
authors.initials: SJ
authors.lastname: Soenen
authors.affiliation: *Institute of Life Science, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK, Department of Medicine, Biomedical NMR Unit-MoSAIC, KU Leuven, B-3000 Leuven, Belgium and Institute for Materials Research, SCaPE, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al-Ali
authors.affiliation: *Institute of Life Science, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK, Department of Medicine, Biomedical NMR Unit-MoSAIC, KU Leuven, B-3000 Leuven, Belgium and Institute for Materials Research, SCaPE, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Andy
authors.initials: A
authors.lastname: Brown
authors.affiliation: *Institute of Life Science, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK, Department of Medicine, Biomedical NMR Unit-MoSAIC, KU Leuven, B-3000 Leuven, Belgium and Institute for Materials Research, SCaPE, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Nicole
authors.initials: N
authors.lastname: Hondow
authors.affiliation: *Institute of Life Science, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK, Department of Medicine, Biomedical NMR Unit-MoSAIC, KU Leuven, B-3000 Leuven, Belgium and Institute for Materials Research, SCaPE, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: John
authors.initials: J
authors.lastname: Wills
authors.affiliation: *Institute of Life Science, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK, Department of Medicine, Biomedical NMR Unit-MoSAIC, KU Leuven, B-3000 Leuven, Belgium and Institute for Materials Research, SCaPE, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Gareth J S
authors.initials: GJ
authors.lastname: Jenkins
authors.affiliation: *Institute of Life Science, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK, Department of Medicine, Biomedical NMR Unit-MoSAIC, KU Leuven, B-3000 Leuven, Belgium and Institute for Materials Research, SCaPE, University of Leeds, Leeds LS2 9JT, UK s.h.doak@swansea.ac.uk.
authors.forename: Shareen H
authors.initials: SH
authors.lastname: Doak
mesh_terms: D019187:Cadmium Compounds / Q000737:chemistry* / Q000633:toxicity; D002460:Cell Line; D005434:Flow Cytometry; D006801:Humans; D017348:Microscopy, Electron, Scanning Transmission; D045663:Quantum Dots; D018036:Selenium Compounds / Q000737:chemistry* / Q000633:toxicity; D013440:Sulfides / Q000737:chemistry* / Q000633:toxicity; D017967:Zinc Compounds / Q000737:chemistry* / Q000633:toxicity
chemical_list: D019187:Cadmium Compounds; D018036:Selenium Compounds; D013440:Sulfides; D017967:Zinc Compounds; C058667:cadmium selenide; C031238:zinc sulfide
keywords: cell type; cellular uptake; cytotoxicity, genotoxicity; nanoparticle; quantum dots