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Pre-Clinical Development of Best-in-Class Zn0.4Fe2.6O4 Magnetic Nanoparticles for Thermal Treatment of Brain Glioblastoma

Kasparis, Georgios; (2021) Pre-Clinical Development of Best-in-Class Zn0.4Fe2.6O4 Magnetic Nanoparticles for Thermal Treatment of Brain Glioblastoma. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Nanomaterials are intensely researched and developed for a wide range of applications. The focus of this work is on developing novel nanomaterials with augmented physicochemical properties for biomedical applications. Specifically, developing magnetic nanoparticles for thermal treatment of neoplasms as this method offers a potentially drug-free approach to cancer treatment currently approved for clinical use for a limited number of malignancies and undergoing further trials for assessing its effect on others. To date, several procedures have been established to produce nanoparticles with variable shapes, sizes and compositions and their effect on various technologies are intensely investigated. Among both anisotropic and isotropic magnetic nanoparticles synthesised as part of this work, superparamagnetic zinc doped ferrite nanoparticles were the most suitable for further development owing to their high magnetisation, superparamagnetic nature, low anisotropy and biocompatibility as characterised by their chemical and physical attributes and compared with iron oxide nanoparticles of same size and morphology. These nanoparticles have been developed using liquid chemistry routes under high temperature and pressure. Their extensive characterisation renders them as the best-in-class nanoparticles in terms of their magnetic properties and size exceeding the magnetic properties of the next most magnetic zinc ferrite synthesised to date whilst having ten times smaller magnetic volume. Their ability to convert magnetic energy to heat (magnetothermal) and light to heat (photothermal) has been assessed with photothermia being far more efficient than magnetothermia both in suspension and in cellular confinement. Magnetothermal conversion was similar to other superparamagnetic materials and of limited clinical use while photothermal conversion showed enhanced performance achieving complete cell death in 10 minutes using clinically relevant settings. The nanoparticles showed extensive cellular uptake in vitro on brain glioblastoma cells as indicated by imaging and magnetometry. The biocompatibility of the nanoparticles has been assessed with several techniques to assess mitochondrial function, cell membrane integrity and clonogenicity indicating a well-tolerated material of similar toxicity to iron oxide which itself is cleared for medical use by the Food and Drug Administration and the European medicines Agency. A practical treatment time has been determined to induce preferentially irreversible apoptosis than necrosis in in vitro experiments as a result of apoptosis-related proteins expression or inhibition and reactive oxygen species formation before, during and after thermal treatment. Biodistribution studies made use of nuclear medicine tomographic imaging techniques to monitor the biodistribution profile of the nanomaterial in real-time including positron emission tomography and single photon emission computed tomography integrated with computed tomography on physiological and immunocompromised mice via intravenous and intranasal administration. The nanomaterial mainly accumulates in organs involved in the clearance pathway; the liver and the kidneys with a small amount of material reaching the brain.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Pre-Clinical Development of Best-in-Class Zn0.4Fe2.6O4 Magnetic Nanoparticles for Thermal Treatment of Brain Glioblastoma
Event: UCL
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10131416
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