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Title: Formulation of cerium oxide nanoparticles towards the prevention and treatment of cataract
Author: Hanafy, Belal I.
ISNI:       0000 0004 9355 161X
Awarding Body: Nottingham Trent University
Current Institution: Nottingham Trent University
Date of Award: 2020
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Chronic diseases are rising in incidence and prevalence because of the increase in life expectancy in many parts of the world and the advances in medicine that manage disease progression, rather than curing and alleviating the causes. Cataract is one such chronic condition. Identifying a therapeutic intervention that is successful in reversing or preventing cataracts may have applications for other chronic diseases of protein misfolding, such as diabetes and Alzheimer's disease as these have similar causation factors, notably oxidative stress and/or glycation. To date, surgery remains the only effective treatment for cataract and the search for alternatives is still ongoing. Cerium oxide nanoparticles (nanoceria) which have antioxidant, radioprotective and enzyme-mimetic properties have the potential to lead to an effective non-surgical treatment. However, nanoceria stability in physiological media is poor thus hindering their effective use in biomedical applications. In the work described in this thesis, a highly efficient one-pot synthesis of nanoceria (2–5 nm) has been achieved. The nanoparticles were coated with a novel hybrid coating (ethylene glycol, ethylene glycol monoand di- acetates) providing the formulation with superior colloidal stability in physiological media. The ethylene glycol coated nanoceria formulation (EGCNPs), up to concentrations of 200 μg/ml, is not toxic to human lens epithelial cells and has no adverse effect on the cellular morphology, proliferation rate, mitochondrial morphology, mitochondrial membrane potential, ATP level, DNA integrity and basal reactive oxygen species (ROS) level. Exceeding the safe concentration of nanoceria leads to genotoxicity and apoptotic cell death mediated by ROS elevation and mitochondrial damage, a mechanism which is comprehensively investigated for the first time in human lens epithelial cells (HLECs). EGCNPs uptake in HLECs was found to be endocytosisdependent and the nanoparticles localised extensively in the mitochondria. This localisation has enabled the nanoparticles to protect HLECs against oxidative stress, act as a catalase mimetic and increase reduced glutathione/oxidised glutathione ratio (GSH/GSSG). Furthermore, it is shown for the first time that these nanoparticles can protect lens proteins against glucose-induced glycation that is a major cause of cataract particularly in diabetics. Together, these results demonstrate great potential for nanoceria in protecting against cataract and should be taken to in-vivo studies.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available