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Title: Development of a novel targeted nanotherapy for the treatment of melanoma
Author: Webster, Carl
ISNI:       0000 0004 6058 8168
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2016
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Nanoparticles have been utilised in a wide range of applications and they provide unique advantages as drug delivery carriers and imaging agents in biomedicine. In particular, nanoparticles have been employed as therapeutic systems in oncology to overcome the limitations of conventional chemotherapeutics. Melanoma is the cancer of pigment-producing cells in the basal layer of the epidermis. Once metastasised, melanoma is highly aggressive and notoriously difficult to treat with the currently available therapies. In order to improve the therapeutic options available for the treatment of melanoma, we developed iron oxide nanoparticles for use as a melanoma-specific drug delivery system. Iron oxide nanoparticles are useful tools in oncology as their superparamagnetic properties allow them to be used as a delivery system capable of acting as both an imaging contrast agent and a magnetic hyperthermia therapy agent. Here, we developed a targeted iron oxide nanoparticle that exploits the overexpression of melanocortin 1 receptor, which is upregulated on the cell surface of melanoma cells. Surface functionalisation of iron oxide nanoparticles with the melanocortin 1 receptor agonist, α-melanocytes stimulating hormone, increased internalisation of nanoparticles in melanoma cells compared to non-melanoma and melanocyte cell lines. Moreover, the cytotoxic drug paclitaxel, was successfully encapsulated into the outer shell of the nanosystem. Delivery of paclitaxel via melanoma targeted iron oxide nanoparticles led to dose dependent cytotoxicity in melanoma cells. A major limitation in the application of novel nanosystems in the clinic is the lack of an accurate and substantial toxicity assessment at the early stages of development. We addressed this issue by developing a hazard assessment protocol that combines cytotoxicity data with an embryonic vertebrate phenotypic assay to produce an overall toxicity index. Our iron oxide nanoparticle was assessed using this toxicity methodology to confirm they induced no toxic effects, and so were validated for further developed to be used as a therapeutic system.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available