Artur Filipe Rodrigues
University of Manchester
Filipe is a PhD student at the Nanomedicine Lab, based at University of Manchester, UK. After he worked on the production and characterisation of graphene oxide sheets with different lateral dimensions, he is now studying the biological impact of graphene oxide sheets in vivo, with a main interest on the impact in the respiratory system.
Graphene oxide (GO) is a graphene-based material that has attracted commercial interest in a wide range of applications, from inks and spray coatings to drug delivery. Understanding the toxicological profile of GO is crucial for this implementation to occur. A number of studies have discussed the toxicity of GO flakes, but the in vivo impact of their lateral dimensions is still not clear. Our group has previously demonstrated that GO flakes of small lateral dimensions (s-GO, < 1 µm) do not trigger significant inflammation after intraperitoneal injection.
Here, we investigated the impact of GO flakes of large, micrometre-sized lateral dimensions (l-GO, 1 to 20 µm) after i.p. injection, to test whether high aspect ratio nanomaterials such as l-GO have a more deleterious impact than their smaller counterparts. We also aimed to address whether a protein corona would alter the biological response by testing different dispersing modalities (0.5% BSA in saline solution vs 5% dextrose in water).
Using SPECT/CT imaging, we observed that both GOs were able to travel towards the peritoneal mesothelium of the diaphragm. The presence of GO was confirmed by Raman mapping of diaphragm histological sections obtained 1 and 7 days after injection. Histology and SEM analyses showed that GO did not induce significant recruitment of granulocytes to the mesothelium, irrespective of their size and dispersion.
We then characterised the potential of these materials to induce inflammation by differential staining of cells extracted from the peritoneal cavity. We observed that s-GO pre-dispersed in 5% dextrose elicited a greater recruitment of monocytic cells in the peritoneal cavity 24 h after injection, which coincided with their greater ability to be internalised. However, when it was pre-coated with BSA proteins, the recruitment of immune cells by s-GO was reduced.
In conclusion, GO flakes did not induce mesothelial granuloma irrespective of their lateral dimensions and dispersion. But s-GO triggered monocytic cell recruitment in the peritoneal cavity in the absence of protein pre-coating. These results highlight the importance of a bio-corona in the surface reactivity of GO flakes towards biological systems.
