Exploring the cytotoxicity of DNA nanopores for treatment of Melanoma

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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Identifiers

ORCID for Eugen Stulz: orcid.org/0000-0002-5302-2276

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