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First XM2 PhD thesis submission by Tanveer Tabish: Development of graphene nanostructures for use in anti-cancer nanomedicine
Tanveer Tabish is the first XM2 PGR to submit his PhD thesis (15 February 2018). Please see the abstract of his thesis below. Tanveer is supervised by Shaowei Zhang and Yongde Xia and he published more than 10 journal articles and conference proceedings during his time in the CDT for Metamaterials, for example in the International Journal of Nanomedicine, Nanotechnology, Redox Biology, Scientific Reports, and at the IEEE Nanotechnology Materials and Devices conference (2016), respectively. Tanveer spent 3 months on a research visit at the Politecnico di Milano (Italy) in 2017, and arranged multiple short-term research stays with collaborators at the University of Oxford, King’s College London, and the University of Newcastle. He went to various national and international conferences and workshops, for example in Oxford (UK), Antalya (Turkey), Toulouse (France) and Chennai (India) where he presented his work via posters and presentations. Tanveer won a presentation prize at the 22nd CSCST-SCI Conference for Renewable energy and novel materials for a sustainable future (Birmingham, 2015) and gave an invited talk on “Fabrication of graphene nanopres for application in marine biology” at a workshop organized by British Council and Royal Society of Chemistry the at the Middle East Technical University in Ankara (Turkey, 2017) .
We are incredibly proud of Tanveer and hope he will be successful with his applications to embark on a career in academia in the UK.
Well done Tanveer!
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PhD thesis abstract Tanveer Tabish: DEVELOPMENT OF GRAPHENE NANOSTRUCTURES FOR USE IN ANTI-CANCER NANOMEDICINE
Figure 1: Schematic illustration of the potential mechanisms by which reactive oxygen species (ROS) are associated with the cellular toxicity of graphene. Graphene may affect biological behavior at the cellular, subcellular, protein and gene levels. The deposition, distribution and clearance of graphene after entering into a living system is a major knowledge gap in understanding the toxicity of graphene. Graphene circulating in the bloodstream is internalized into cells through the plasma membrane. The plasma membrane is a selectively permeable membrane that transfers materials such as ions and nano-sized proteins. Graphene (depending on its size, shape, and surface chemistry) enters the cell via different pathways such as clathrin/caveolar-mediated endocytosis, phagocytosis, macropinocytosis, and pinocytosis and exits the cell via the pathways of lysosome secretion, vesicle-related secretion, and non-vesicle-related secretion. Graphene-induced ROS may cause oxidative stress, loss of cell function, mitochondrial damage, initiation of lipid peroxidation, covalent chemical modifications of nucleic acids, DNA-strand breaks, induction of gene expression via the activation of transcription factors, and modulation of inflammation via signal transduction – leading to toxicity, cell death and genotoxicity. [With permission of Elsevier, Oxford; ‘Tabish, T. A., Zhang, S., & Winyard, P. G. (2018). Developing the next generation of graphene-based platforms for cancer therapeutics: The potential role of reactive oxygen species. Redox biology. 15, 34-40]Nanomedicine utilises biocompatible nanomaterials for therapeutic as well as imaging purposes, for the treatment of various diseases including cancer, neurological disorders and wound infections. Graphene, a material composed of a single layer of carbon atoms, has recently shown great potential to improve diagnostics and therapeutics, owing to its small size, large surface-area-to-volume ratio and unique physicochemical properties. However, the limited fabrication, in vitro and in vivo functionalities published in the literature indicate inconsistencies regarding the factors affecting metabolic fate, biodistribution as well as toxicity patterns of graphene. This thesis focuses on the biological effects of graphene-based materials, including graphene oxide (GO), reduced graphene oxide (rGO), graphene nanopores (GNPs), graphene quantum dots (GQDs) and three-dimensional graphene foam (GF). These can be used to closely mimic therapeutic functions and thereby open up new pathways to anticancer nanomedicine. In this work, a biocompatible GO-based anti-metastatic enzyme cancer therapy approach has been introduced for the first time to target the extracellular pro-metastatic and pro- tumourigenic enzymes of cathepsin D and cathepsin L, which are typically overexpressed in ovarian and breast cancers. Definitive binding and modulation of cathepsin- D and -L with GO has revealed that both of the enzymes were adsorbed onto the surface of GO through its cationic and hydrophilic residues under the biologically relevant condition of acidic pH. It has been demonstrated that low concentrations of rGO were shown to significantly produce late apoptosis and necrosis rather than early apoptotic events in lung cancer cells (A549 and SKMES-1), suggesting that it was able to disintegrate the cellular membranes in a dose-dependent manner. GNPs at lower concentrations (250µg/ml) induce upregulation of phosphatidylserine on cell surface membrane (i.e. early apoptotic event), which does not significantly disintegrate the cell membrane in the aforementioned lung cancer cells, while higher concentrations of GNPs (5 and 15 mg/kg) in rats (when intraperitoneally injected) exhibited sub-chronic toxicity in a period of 27 days. The interaction of GQDs and trypsin has revealed the strong bonding capacity of GQDs with trypsin, owing to their surface charge and surface functionalities evidencing the high bioavailability of GQDs in enzyme engineering. Finally, 3D GF was developed to probe the role of graphene-based scaffold cues in the field of regenerative medicine revealing their cell attachment to in vitro cell cultures. Furthermore, GF was shown to maintain remarkable biocompatibility with in vitro and in vivo toxicity screening models when exposed for 7 days at doses of 5, 10 and 15 mg/l. Taken together, graphene and its modified structures developed in this thesis promise to revolutionise clinical settings across the board in nanomedicine which include, but are not limited to, ultra-high sensitive enzyme adsorbents, high throughput biosensors, enzyme modulators and smart scaffolds for tissue regeneration.
Tanveer Tabish is the first XM2 PGR to submit his PhD thesis (15 February 2018). Please see the abstract of his thesis below. Tanveer is supervised by Shaowei Zhang and Yongde Xia and he published more than 10 journal articles and conference proceedings during his time in the CDT for Metamaterials, for example in the International Journal of Nanomedicine, Nanotechnology, Redox Biology, Scientific Reports, and at the IEEE Nanotechnology Materials and Devices conference (2016), respectively. Tanveer spent 3 months on a research visit at the Politecnico di Milano (Italy) in 2017, and arranged multiple short-term research stays with collaborators at the University of Oxford, King’s College London, and the University of Newcastle. He went to various national and international conferences and workshops, for example in Oxford (UK), Antalya (Turkey), Toulouse (France) and Chennai (India) where he presented his work via posters and presentations. Tanveer won a presentation prize at the 22nd CSCST-SCI Conference for Renewable energy and novel materials for a sustainable future (Birmingham, 2015) and gave an invited talk on “Fabrication of graphene nanopres for application in marine biology” at a workshop organized by British Council and Royal Society of Chemistry the at the Middle East Technical University in Ankara (Turkey, 2017) .