Toxicological assessment of graphene based nanomaterials in cell culture models

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Elhaneid, Mohamed (2019). Toxicological assessment of graphene based nanomaterials in cell culture models. University of Birmingham. Ph.D.

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Abstract

Graphene oxide (GO) and reduced GO (r-GO) nanomaterials exhibit great potential for several biomedical applications. Of foremost importance is to determine any potential health hazards related in their exposure. In this research, we hypothesised that the different material properties evidenced by GO and r-GO would elicit different biological responses. The first objective of this work was to synthesize Go and r-GO and characterize their physiochemical properties. The second aim was to investigate whether the two-distinct surface chemistries of GO and r-GO influenced their biological effect. The potential toxicity of these nanomaterials was investigated using the normal lung fibroplast cell line MRC-5 and cancerous epithelial lung cell line A549. The cytotoxicity of graphene derivatives was concentration-, time- and cell-dependent and varied according to the material used. Thus, the surface chemistry of graphene plays a critical role in its biocompatibility. Non-cancerous cells had a higher sensitivity to GO cytotoxicity than cancer cells. R-GO was highly biocompatible to MRC-5 cells and for A549 cells had a minimal effect of cell viability. At 37C˚, GO and r-GO were moderately hemolyric at concentration of 125 µg/ml and highly haemolytic at concentration of 300 µg/ml. Exposure of cells to both graphene derivatives led to reactive oxygen species (RO5) generation without genotoxicity. GO, but not r-GO, led to autophagy in both cell lines, possibly inhibiting the PIP3-Akt/mTOR pathway. For both cell lines and at non-lethal concentrations, GO downregulated the expression of glycogen synthase kinase-3 (GSK-3ß). GO was also found to dysregulate both Wnt/b-catenin and Akt cell signalling pathways which are vital for cellular function. The finding relating to cell signalling provide an insight to the safety of GO which is important to its use in cancer therapy.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):