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Title: Synthesis, functionalisation, and biomedical application of phospholipid-functionalised gold nanorods for cancer therapy
Author: Roach, Lucien Frederick Alexander
ISNI:       0000 0004 8501 0645
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2019
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Cancer is the most common cause of death in the UK. Due to its aging population, the rate of cancer diagnoses is expected to rise dramatically in the coming decades. Currently cancer treatments have harsh side effects that cannot be well tolerated by the elderly, hence there is a need to develop new methods of cancer therapy which offer substantially better patient experiences. One such route is the use of near infrared--absorbent gold nanorods (AuNRs), which offer suitable optical and thermal properties to enable their use in techniques such as photothermal therapy and photoacoustic imaging. In this thesis we will explore the use of AuNRs in these roles as agents in cancer therapy. This is addressed in three core areas; firstly the seedless production of AuNRs using binary surfactants. It is demonstrated how the morphology and optical properties of such particles can be manipulated through the inclusion of a co-surfactant. As well as yielding improvements in the monodispersity, shape yield and scalability of the protocol. Secondly, the surface functionalisation of AuNRs with phospholipids, we demonstrate the effective removal of CTAB, a toxic surfactant used in the synthesis, this is demonstrated through the use of ¹H nuclear magnetic spectroscopy, surface enhanced Raman spectroscopy and pH-dependent zeta potential measurements, this is present alongside stability studies of AuNRs of different coating, demonstrating the improved stability of AuNRs prepared with phospholipids. Finally, the application of phospholipid-coated AuNRs in cancer therapy is explored. We show that these particles are non--toxic in vitro and in vivo. We also explore their efficacy as photothermal conversion agents, measuring the achievable temperature rises under CW illumination, as well as imaging them using multispectral optoacoustic tomography of the particles in phantoms. In vivo measurements of the effects of heating these AuNRs under CW and nanosecond lasers on human carcinoma cell lines were also investigated. Finally the biodistribution of these particles was explored, when passively targeted or functionalised with cancer specific adhirons though ICP-MS analysis of ex vivo murine samples.
Supervisor: Evans, Stephen D. ; Critchley, Kevin ; Coletta, P. Louise Sponsor: University of Leeds
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available