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Title: Novel embolic particles for cancer therapy
Author: Morrison, Rachel Anne
ISNI:       0000 0004 6496 2751
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2016
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The aim of this thesis was to develop novel embolic particles for cancer therapy using a combination of nano and microparticles. The particles have been designed and synthesised to have a polystyrene core, be radiopaque, act as a radiosensitiser and have a high capacity for loading of chemotherapy drugs. The polystyrene core has been designed so it effectively blocks the tumour vasculature thereby limiting oxygen and nutrient delivery to the tumour thus causing tumour necrosis. The core of the polystyrene particle incorporates tantalum oxide nanoparticles to provide X-ray contrast to the embolic microparticles. The surface of the polystyrene particle has been coated with rare earth doped titanium dioxide (TiO2) nanoparticles which produce reactive oxygen species upon X-ray activation. This allows the embolic particle to act as a radiosensitising agent and has been shown to reduce cell proliferation in the presence of X-rays. The surface of the polystyrene particles has also been coated with mesoporous SiO2 nanoparticles which allow for the high loading capacity of chemotherapeutic drugs. This permits chemotherapy to be delivered directly to the tumour location, thereby reducing the toxic side effects of systemic treatment. As a proof of concept, the chemoembolization particles have been loaded with a novel fungal derived chemotherapeutic Ophiobolin A and the controlled release has been demonstrated. The OphA chemoembolization particles reduced cell viability by approximately 70% compared to the blank chemoembolization particles. The mechanism of cell death of OphA on eight cancer cell lines and one control cell line has also been studied and its effect on cellular organelles elucidated. OphA shows great promise as a novel chemotherapeutic which could be taken forward to animal trials.
Supervisor: Townley, Helen ; Dobson, Peter ; Noble, Julia Alison Sponsor: RCUK Digital Economy Fund
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available