Graphene-based enrichment of the urine proteome

Abstract

Witnessing a decade since the Physics Nobel Prize awarding for the ground breaking studies on the “two-dimensional material graphene", graphene oxide (GO) stands as a promising candidate under the spotlight of biomedical research. Amongst the most questioned applications lies the possibility of its future use for intravenous (IV) treatment, imaging, diagnostic or theranostic purposes. Numerous studies are highlighting the trade-off between the physicochemical properties of GO materials and their in vivo safety, biodistribution and performances. However, little is known about the in vivo interaction of GO with biofluids. To date, no study investigated the interactions of GO with proteins upon their IV administration. This is a major gap, as it has been shown that the adsorption of blood proteins on the surface of nanoparticles can modulate their in vivo effects and fate. Our group and others have found that GO flakes are able to travel from blood to bladder, without causing renal impairment. In this thesis, we show that renal excretion could be explored to recover protein-coated GO flakes after their IV administration. We developed a robust method to simultaneously recover GO and remove free proteins from urine. Our results suggest that the proteomic content of mouse urine is enriched upon GO excretion. Further on, inspired by the proteomic studies in our laboratory showing that in vivo protein-coated nanoparticles can be explored as a disease biomarker resource, we questioned the possibility of using our method for scavenging disease-related proteins. Using B16-F10 melanoma tumour bearing mice, we provided evidence that the excretion of GO boosts the levels of disease-relevant molecules into the urine samples. In summary, this project reveals a new method for the in vivo GO-protein interaction studies and disease biomarker scavenging.

Date of Award	1 Aug 2021
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Anthony Whetton (Supervisor), Anthony Freemont (Supervisor) & Kostas Kostarelos (Supervisor)