Graphene oxide and hexagonal boron nitride nanosheets do not induce innate immune memory

Alexander Fordham, Alberto Bianco, Neus Lozano, Kostas Kostarelos, Cyrill Bussy

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review


Engineered 2D nanomaterials such as graphene oxide (GO) and hexagonal boron nitride (hBN) are an emerging but growing aspect of human technology. However, research is still inconclusive on the respiratory system response to such 2D materials. One area of recent concern is the generation of innate immune memory (IIM). Innate imprinting can be defined as the acquisition by innate cells of memory like characteristics in the form of epigenetic modifications. If triggered, these modifications may induce altered immune responses to environmental stimuli, such as allergens, engineered nanomaterials or air pollution related particles. These altered responses could result in detrimental consequences for those environmentally exposed and for therapeutic applications.

In the present study bone marrow derived macrophages (BMDM) were exposed for 24 h to either GO or hBN, and then re-exposed to the same materials after 5 days. Cytokine secretion, uptake, gene expression and epigenetic markers were then measured to determine the generation of inflammation and IIM related epigenetic modifications. Raman mapping and confocal microscopy indicated that both materials were being taken up by BMDM in detectable quantities. However, GO did not induce inflammation or IIM in BMDM upon multiple exposures. In addition, exposure to GO did not change the response of BMDM to secondary stimuli such as lipopolysaccharide and β-glucan. On the other hand, hBN induced an inflammatory response associated to iNOS-related pathways after both one and multiple exposures. Nevertheless, analysis of the epigenetics after hBN exposure did not indicate the significant presence of epigenetic markers related to IIM.

It was concluded that for direct in vitro exposure, endotoxin free GO could be considered ‘inert’ eliciting no detectible response from BMDM. In contrast endotoxin free hBN can induce an inflammatory state in BMDM but not any long-term epigenetic modifications related to IIM. The lack of long-term epigenetic responses is a beneficial outcome for the overall safety of the materials. It suggests that the innate system response would not change over repeated long-term but low dose exposures to 2D materials, as would be expected in an occupational exposure scenario. These results provide further understanding of the safety profile of 2D materials at a time when their applications in consumer products is growing at fast pace.
Original languageEnglish
Title of host publicationToxicology Letters
PublisherElsevier BV
Number of pages1
Editionsupplement 1
Publication statusPublished - 12 Sept 2022
EventAbstracts of the XVIth International Congress of Toxicology (ICT 2022) - UNITING IN TOXICOLOGY - Maastricht, Netherlands
Duration: 18 Sept 202221 Sept 2022


ConferenceAbstracts of the XVIth International Congress of Toxicology (ICT 2022) - UNITING IN TOXICOLOGY


  • graphene
  • 2D materials

Research Beacons, Institutes and Platforms

  • Advanced materials
  • National Graphene Institute


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  • CDT in Science and Applications of Graphene and Related Nanomaterial

    Grigorieva, I., Burnett, H., Cusworth, E., Deaconu, D., Dumitriu-Iovanescu, A., Kang, Y., Little, J., Rees, E., Selles, F., Shaker, M., Soong, Y., Swindell, J., Tainton, G., Wood, H., Astles, T., Carl, A., Chen, G., Richard De Latour, H., Dowinton, O., Haskell, S., Hills, K., Hoole, C., Huang, Y., Kalsi, T., Powell, L., Quiligotti, K., Rimmer, J., Smith, L., Thornley, W., Yang, J., Young, W., Zhao, M., Al Busaidi, R., Al Ruqeishi, E., Chadha, A., Chen, M., Dennis, G., Dunn, E., Gamblen, E., Gao, Y., Georgantas, Y., Jiang, Z., Karakasidi, A., Mcellistrim, A., Meehan, M., Okwelogu, E., Taylor, M., Wang, W., Xin, B., Castle, C., Clout, P., Dean, S. D., Fordham, A., Griffin, E., Hardwick, T., Hawkins-Pottier, G., Jones, A., Lewthwaite, K., Monteil, S., Moulsdale, C., Mullan, C., Orts Mercadillo, V., Sanderson, D., Skliueva, I., Skuse, C., Steiner, P., Winstanley, B., Barry, D., Brooks, D., Cai, J., Chen, Y., Chen, C., Draude, A., Emmerson, C., Gavriliuc, V., Greaves, M., Higgins, E., Mcmaster, R., Mcnair, R., O'Brien, C., Peasey, A., Pinter, G., Shao, S., Thomas, D., Thomas, D., Tsim, L. T. B., Wengraf, J., Weston, A., Yu, T., De Libero, H., Chan, K. C., Tan, Y. T. & Thomson, T.


    Project: Other

  • Graphene Flagship Core 3

    Kostarelos, K., Bussy, C., Coope, D. & Vranic, S.


    Project: Research

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