Graphene-based materials (GBM) have recently generated great interest due to their unique two-dimensional (2D) carbon geometry, which confers exceptional physicochemical properties that hold great promise in many fields, including biomedicine. An understanding of how these novel 2D materials interact with the biological milieu is therefore fundamental for their development and use. Graphene oxide (GO) has been proven more biologically friendly than the highly hydrophobic pristine graphene. Therefore, the main aim of this study was to prepare well-characterised GO derivatives and test the hypothesis of their possible use for biomedical applications. GO was prepared reproducibly by a modified Hummers' method and further functionalised by using a radio-metal chelating agent, namely 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to form GO-DOTA. The constructs were extensively studied using structural, optical and surface characterisation techniques. GO prepared from different forms of graphite demonstrated differences mainly in structure and production yields. However, all GO constructs were found biocompatible, with the mammalian cell cultures tested; furthermore, the biocompatibility of GO prepared as papers was retained when they were used as substrates for cell growth. Radiolabelling of GO-DOTA was further carried out to yield highly stable radio-labelled constructs, both in vitro and in vivo. These constructs were used for in vivo whole-body imaging and biodistribution studies in mice after intravenous administration. Extensive urinary excretion and accumulation mainly in the reticuloendothelial system (RES), including the spleen, liver and lungs, was the main fate of all the GO derivatives used in this thesis. The physicochemical characteristics were determined to play a central role for their preferential fate and accumulation. While the thicker sheets tended to accumulate mainly in the RES, the thinner ones were mostly excreted via the kidneys. Finally, it was crucial to perform safety investigations involving the structure and function of organs at high risk of injury (mainly the kidney and spleen). Our results revealed that no severe structural damage or histopathologic or functional abnormality of these vital organs. However, some preliminary inflammatory responses were detected that require further investigation. In summary, this study helped gain a better understanding of how thin 2D materials interact with biological barriers and the results indicate that these materials could be potential candidates for biological applications. Nevertheless, further investigations are necessary to confirm our findings.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:719288 |
| Date | January 2016 |
| Creators | Jasim, Dhifaf |
| Contributors | Kostarelos, Kostas |
| Publisher | University of Manchester |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://www.research.manchester.ac.uk/portal/en/theses/graphene-oxide-derivatives-for-biomedical-applications(83c552dc-50f6-4771-95b4-d1aace0db493).html |
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