Development of a novel targeted nanotherapy for the treatment of melanoma

Webster, Carl (2016) Development of a novel targeted nanotherapy for the treatment of melanoma. Doctoral thesis, University of East Anglia.

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Abstract

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.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Pharmacy
Depositing User: Katie Miller
Date Deposited: 22 Feb 2017 10:32
Last Modified: 22 Feb 2017 10:32
URI: https://ueaeprints.uea.ac.uk/id/eprint/62677
DOI:

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