Journal of Nanoparticle Research

, 14:1069 | Cite as

Comparative effects of metal oxide nanoparticles on human airway epithelial cells and macrophages

  • Bianca Maria Rotoli
  • Ovidio Bussolati
  • Anna Luisa Costa
  • Magda Blosi
  • Luisana Di Cristo
  • Pier Paolo Zanello
  • Massimiliano G. Bianchi
  • Rossana Visigalli
  • Enrico BergamaschiEmail author
Research Paper
Part of the following topical collections:
  1. Nanotechnology, Occupational and Environmental Health


Among nanomaterials of industrial relevance, metal-based nanoparticles (NPs) are widely used, but their effects on airway cells are relatively poorly characterized. To compare the effects of metal NPs on cells representative of the lung-blood barrier, Calu-3 epithelial cells and Raw264.7 macrophages were incubated with three industrially relevant preparations of TiO2 NPs (size range 4–33 nm), two preparations of CeO2 NPs (9–36 nm) and CuO NPs (25 nm). While Raw264.7 were grown on standard plasticware, Calu-3 cells were seeded on permeable filters, where they form a high-resistance monolayer, providing an in vitro model of the airway barrier. Metal NPs, obtained from industrial sources, were characterized under the conditions adopted for the biological tests. Cytotoxicity was assessed with resazurin method in both epithelial and macrophage cells, while epithelial barrier permeability was monitored measuring the trans-epithelial electrical resistance (TEER). In macrophages, titania and ceria had no significant effect on viability in the whole range of nominal doses tested (15–240 μg/cm2 of monolayer), while CuO NPs produced a marked viability loss. Moreover, only CuO NPs, but not the other NPs, lowered TEER of Calu-3 monolayers, pointing to the impairment of the epithelial barrier. TEER decreased by 30 % at the dose of 10 μg/cm2 of CuO NPs, compared to untreated control, and was abolished at doses ≥80 μg/cm2, in strict correlation with changes in cell viability. These results indicate that (1) CuO NPs increase airway epithelium permeability even at relatively low doses and are significantly toxic for macrophages and airway epithelial cells, likely through the release of Cu ions in the medium; (2) TiO2 and CeO2 NPs do not affect TEER and exhibit little acute toxicity for airway epithelial cells and macrophages; and (3) TEER measurement can provide a simple method to assess the impairment of in vitro airway epithelial barrier model by manufactured nanomaterials.


Copper oxide Titanium oxide Cerium oxide Airway epithelium Nanoparticles 



Supported by the EU-funded research project ‘Safe Nano Worker Exposure Scenarios’—SANOWORK (Grant No. FP7-280716). We thank Mr. Paul Reip (Intrinsiq Materials Ltd., Cody Technology Park, Ively Road, Farnborough—Hampshire, UK) and Prof. Lucia Migliore, University of Pisa, for CuO NPs.

Supplementary material

11051_2012_1069_MOESM1_ESM.docx (616 kb)
Supplementary material 1 (DOCX 617 kb)


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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Bianca Maria Rotoli
    • 1
  • Ovidio Bussolati
    • 1
  • Anna Luisa Costa
    • 3
  • Magda Blosi
    • 3
  • Luisana Di Cristo
    • 2
  • Pier Paolo Zanello
    • 1
  • Massimiliano G. Bianchi
    • 1
  • Rossana Visigalli
    • 1
  • Enrico Bergamaschi
    • 4
    Email author
  1. 1.Department of Experimental MedicineUniversity of ParmaParmaItaly
  2. 2.Department of Pharmacological, Biological and Applied Chemical SciencesUniversity of ParmaParmaItaly
  3. 3.Institute of Science and Technology for CeramicsNational Research CouncilFaenzaItaly
  4. 4.Unit of Occupational Medicine, Department of Clinical Medicine, Nephrology and Health SciencesUniversity of ParmaParmaItaly

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