Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.705138
Title: Nanoparticles for the selective delivery of photosensitisers for photodynamic cancer therapy
Author: Garcia Calavia, Paula
ISNI:       0000 0004 6058 8010
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2016
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Abstract:
Photodynamic therapy (PDT) requires a photosensitiser, light and oxygen to generate reactive oxygen species and cell death. The hydrophobicity of photosensitisers can be overcome using nanoparticles. Furthermore, nanoparticles can be functionalised with cancer-specific ligands to increase selectivity towards tumours. The aim of this thesis was to investigate the use of nanoparticles for PDT of breast cancer. Gold nanoparticles (AuNPs) were functionalised with polyethylene glycol (PEG) and a zinc phthalocyanine photosensitiser (Pc). Two Pcs differing in the length of the carbon chain that connects the Pc to the gold, three (C3Pc) or eleven (C11Pc) carbon atoms, were explored. Fluorescence emission intensity was higher for free C11Pc. Conversely, on the surface of the AuNPs, it was higher for C3Pc. The higher fluorescence emission intensity of C3Pc-PEG-AuNPs correlated with an increased production of singlet oxygen (1O2). SK-BR-3 cells internalised both nanosystems but cell death was enhanced with C3Pc-PEG-AuNPs (80 %), due to metal-enhanced fluorescence, as compared to C11Pc-PEG-AuNPs (10 %). The conjugation of the AuNPs with a breast cancer-specific antibody improved the internalisation and PDT efficacy of both nanosystems. The potential use of a carbohydrate, lactose, to target the galectin-1 receptor on breast cancer cells was studied. Lactose and either C3Pc or C11Pc were conjugated to AuNPs. Two breast cancer cell lines, SK-BR-3 and MDA-MB-231, were used. While lactose-C11Pc-AuNPs only induced phototoxicity to SK-BR-3 cells, lactose-C3Pc-AuNPs induced effective PDT for both cell lines. Evidence of targeting galectin-1 was only observed for MDA-MB-231 cells. The use of upconverting nanoparticles (UCNPs) functionalised with the photosensitiser Rose Bengal (RB) for near-infrared PDT was investigated. Energy transfer between the UCNPs and RB upon excitation at 980 nm allowed the generation of 1O2. SK-BR-3 cells successfully internalised the UCNPs and induced effective PDT at 15 μg/mL, leading to minimal dark toxicity and effective cell death following irradiation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.705138  DOI: Not available
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