Safety assessment of graphene-based materials: focus on pulmonary and immune system

B. Fadeel
Karolinska Institutet,
Sweden

Keywords: graphene, GBM, biomedical application, immune system

Summary:

Graphene-based materials (GBMs) are emerging as attractive materials for various biomedical applications (Ferrari et al. Nanoscale. 2015;7:4598-810). Understanding how GBMs interact with the immune system, in particular the innate immune system, is of fundamental importance as phagocytic cells including macrophages, neutrophils, and dendritic cells represent the first line of cellular defense against pathogens and other foreign intrusion. Contradictory results have been reported with regards to the interactions of GBMs such as graphene oxide (GO) with phagocytes. However, recent studies performed with endotoxin-free GO of differing lateral dimensions have shown that these materials are taken up by macrophages without signs of cytotoxicity. No evidence of Toll-like receptor (TLR) activation or production of pro-inflammatory TNF-α was observed. However, GO elicited caspase-dependent IL-1 β expression, a hallmark of inflammasome activation, in macrophages primed with lipopolysaccharide (LPS). On the other hand, GO was found to trigger a size-dependent release of so-called neutrophil extracellular traps (NETs) in primary human neutrophils through a direct effect on plasma membrane lipids including cholesterol. GO was subsequently found to undergo enzymatic degradation in NETs. Hence, immune cells are apparently able to handle GO in the same manner as pathogens. These studies also serve to illustrate cell type-specific immune responses to GBMs and the importance of employing primary cells for such studies. Enzymatic degradation of nanomaterials may have significant implications for nanomedical applications (Bhattacharya et al. Nanomedicine. 2016;12:333-51). Transcriptomics approaches are being increasingly applied to unravel the mechanisms of interactions of nanomaterials with cells and tissues. Recent studies have shown that GO triggers specific, size-dependent transcriptional effects in human lung cells and distinct pathways were activated following short-term versus long-term, i.e., several weeks of exposure. The present lecture will provide an overview of recent studies on the interactions of GO with immune-competent cells, with examples of omics based studies with which to determine perturbations of genes or pathways in exposed cells or tissues. Understanding the biological interactions of GBMs paves the way to safe handling and use of these novel materials.