Characterising Graphene Suspensions for Drug Delivery A thesis submitted to the University of Manchester for the degree of Doctor of Philosophy in the Faculty of Biology, Medicine and Health 2020 Fai A. Alkathiri School of

Abstract

In biomedical applications, one of the most attractive properties of graphene-based materials (GBMs) is their 2D geometry, which maximises the high surface-to-volume ratio characteristic of nanomaterials. That particular property, along with their versatile functionalisation, suggests they may be designed as multifunctional therapeutics carriers. Here, two types of GBMs, including either pristine graphene (PG) or graphene oxide (GO), were prepared to form suspensions suitable for drug delivery. In the first experimental chapter, in search for GRAS excipients to exfoliate PG and stabilise the suspension, three amino acids (valine, tyrosine and tryptophan) were considered both in computer modelling and experimentally. A strong correlation was observed between the amino acid’s hydrophobicity and the existence of at least one aromatic ring in the amino acid to enhance the exfoliation efficacy, both in terms of the suspension’s concentration s and thinness of the flakes. Together, these results suggested amino acids in particular tryptophan may contribute to the preparation of PG suspensions suitable for drug delivery. In the following chapter, building upon the aforementioned study, tryptophan (Trp), di-Trp and tri-Trp peptides were used to form and stabilise PG suspensions which were also used as doxorubicin carriers. Computer modelling and experimental studies revealed that peptides with ample residues e.g. tri-Trp could accommodate more PG flakes in suspension than Trp. Furthermore, tri-Trp PG complexes had the highest drug content and were better at inhibiting the growth of MDA-MB-231 breast cancer cells more than Trp PG complexes. In the final chapter, three preparations of GO, far more thoroughly studied than PG were characterised with traditional methods and, exploiting the intrinsic fluorescence of GO, with 18 raster image correlation spectroscopy. The results suggests GO’s inherent fluorescence can be used to enhance the characterisation of suspensions as fluorescence measurements can be realised in different media e.g. cell media or in presence of excipients. The research discussed herein demonstrated the complexity of applying GBMs in biomedicine as well as their potential for expansion in medical applications, especially in drug delivery supported. Altogether, this work demonstrates the importance of investigating novel approaches to characterising GBMs and has identified strategies that may be developed to enhance biomedical applications of the materials.