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Exploring the cytotoxicity of DNA nanopores for treatment of Melanoma

Exploring the cytotoxicity of DNA nanopores for treatment of Melanoma
Exploring the cytotoxicity of DNA nanopores for treatment of Melanoma
According to Cancer Research UK “incidence rates for melanoma skin cancer are projected to rise by 7% in the UK between 2014 and 2035, to 32 cases per 100,000 people by 2035”1 , showing there will be an increased need for therapeutics for melanoma in the coming years. Current treatments such as chemo- and radiation therapy are nonspecific and carry undesirable side effects, thus new targeted therapies are in dire need. This thesis proposed to use a deoxyribonucleic acid (DNA) nanopore – peptide hybrid that will target melanoma cells, with little collateral damage to surrounding tissues. It has been shown that DNA nanopores produce a cytotoxic effect when embedded into the cell membrane2 . By conjugating DNA nanopores with the known receptor targeting peptide, NAP-amide, a novel melanoma targeted therapy for advanced disease was proposed. DNA nanopores are a simple form of DNA origami, where DNA strands fold into a predetermined shape, utilising the specific interactions of Watson-Crick DNA base pairing. The nanosized particles are formed by combining a custom-designed set of single stranded DNA, some of which can be modified during or after solid phase synthesis. We have modified two different sized (2 nm and 0.8 nm) nanopore constructs which were previously published3, 4 using the hydrophobic compounds, cholesterol and palmitate, and investigated these for cytotoxicity in HEK293T, B16-F10 and FM55- P cells in a proof-of-concept study. Further modifications of a tetraphenyl porphyrin were made for a bi-modal photodynamic therapeutic, not only as hydrophobic anchors but also as photosensitizers in a human melanoma cell line.
University of Southampton
Entwistle, Lauren Lucinda
23264d2c-32e8-45c0-8083-8c0b40da08c9
Entwistle, Lauren Lucinda
23264d2c-32e8-45c0-8083-8c0b40da08c9
Stulz, Eugen
9a6c04cf-32ca-442b-9281-bbf3d23c622d

Entwistle, Lauren Lucinda (2020) Exploring the cytotoxicity of DNA nanopores for treatment of Melanoma. Doctoral Thesis, 203pp.

Record type: Thesis (Doctoral)

Abstract

According to Cancer Research UK “incidence rates for melanoma skin cancer are projected to rise by 7% in the UK between 2014 and 2035, to 32 cases per 100,000 people by 2035”1 , showing there will be an increased need for therapeutics for melanoma in the coming years. Current treatments such as chemo- and radiation therapy are nonspecific and carry undesirable side effects, thus new targeted therapies are in dire need. This thesis proposed to use a deoxyribonucleic acid (DNA) nanopore – peptide hybrid that will target melanoma cells, with little collateral damage to surrounding tissues. It has been shown that DNA nanopores produce a cytotoxic effect when embedded into the cell membrane2 . By conjugating DNA nanopores with the known receptor targeting peptide, NAP-amide, a novel melanoma targeted therapy for advanced disease was proposed. DNA nanopores are a simple form of DNA origami, where DNA strands fold into a predetermined shape, utilising the specific interactions of Watson-Crick DNA base pairing. The nanosized particles are formed by combining a custom-designed set of single stranded DNA, some of which can be modified during or after solid phase synthesis. We have modified two different sized (2 nm and 0.8 nm) nanopore constructs which were previously published3, 4 using the hydrophobic compounds, cholesterol and palmitate, and investigated these for cytotoxicity in HEK293T, B16-F10 and FM55- P cells in a proof-of-concept study. Further modifications of a tetraphenyl porphyrin were made for a bi-modal photodynamic therapeutic, not only as hydrophobic anchors but also as photosensitizers in a human melanoma cell line.

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Thesis for award
Restricted to Repository staff only until 2 June 2022.
Available under License University of Southampton Thesis Licence.
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PTD with approval
Restricted to Repository staff only
Available under License University of Southampton Thesis Licence.

More information

Published date: May 2020

Identifiers

Local EPrints ID: 447426
URI: http://eprints.soton.ac.uk/id/eprint/447426
PURE UUID: 68368e05-ba29-4832-9f4a-4754f519bd82
ORCID for Eugen Stulz: ORCID iD orcid.org/0000-0002-5302-2276

Catalogue record

Date deposited: 11 Mar 2021 17:33
Last modified: 12 Mar 2021 02:39

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Contributors

Author: Lauren Lucinda Entwistle
Thesis advisor: Eugen Stulz ORCID iD

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