Development of DNA Nanopores for New Biotherapeutic Applications

There is an ever increasing demand within biomedicine for more effective control on the nanoscale, specifically with regards to site specific release of molecular cargo. This is fuelled by the demand to minimise off target effects and maximise drug efficacy. Current methods rely on the use of lipid vesicles to increase the blood half-life and maximise the delivery into the cell itself. There has also been the advance of certain DNA architecture “robots” that can selectively sort molecular cargo through specific stimuli. An integral part of the function of DNA nanotechnology is the combination of DNA architectures with lipid membranes/vesicles. Thus there is a demand to be able to manipulate the nano-environment within the body to maximise therapeutic effect. This will further enhance DNA nanotechnology to capitalise on finite control within the body. Previously there has been limited development of “smart sensing”. In this thesis we investigate the development of molecular DNA nanopores that respond to different stimuli: thermosensitive and protein gating, to control the release of molecular cargo for therapeutic effect. Additionally encompassed within this is the research into DNA and lipid interactions whereby understanding the interactions enables the optimum design of DNA nanopores to be realised. In the thesis the newly exploited understanding of the interactions at the molecular level between lipid and DNA give insight to the development of targeted DNA nanostructures. This allowed the development of artificial DNA nanopore that demonstration of the first controlled release of molecular cargo through temperature sensitivity. The effectiveness of the nanodevice and protein specific sensing ability is demonstrated with successful cell killing properties that are enhanced when utilised with the device, compared to the drug alone. The work conducted greatly advances the field of DNA nanotechnology and precision biomedicine