A major challenge for drug delivery is in ensuring that the active agent is delivered to the correct cell types in the correct quantities to induce the desired therapeutic effect. Working closely with our industrial partner Liquid Research Ltd, we will address this challenge by designing magnetic nanoparticles (MNPs) with a thermally-responsive shell for targeted delivery and release of drugs. The idea behind our method is that protein-based drug molecules can be encapsulated in the nanoparticle shell at human body temperature, where their release is triggered by application of an alternating magnetic field which heats the nanoparticles and disrupts the shell. We recently demonstrated the feasibility of our approach [1]. In this project, we aim to develop a new MNP system based on elastin-like peptides (ELPs) [2]. These thermally-responsive materials have much more clinical potential than synthetic polymers used in our previous work. Functional groups at the surface of ELP-coated MNPs will be used for chemical functionalisation, e.g., attachment of an antibody. This exciting new MNP modification will allow us to target delivery of the encapsulated protein to specific tissues. The new MNP system will be applied to the delivery of therapeutic proteins, focusing on bone morphogenetic protein 2 (BMP2) for the treatment of bone disease, an urgent global healthcare need.
Experimental approach
We will synthesise and characterise ELP-coated MNPs using chemical and biochemical methods established in our laboratories and by our industrial partner. Encapsulation and magnetic release of proteins (e.g., BMP2) by these MNPs will be studied in buffers and cell cultures. Bringing chemistry and biology together will help us understand the nature of protein-nanoparticle interactions, which is an important part of the project.
Collaboration with industry
The project is supported by Liquids Research Ltd who is a major supplier of magnetic nanoparticles. The company will fully fund a 3-month placement at their site, will contribute to student training and conference allowance, and will allow us to use their protocols and equipment for nanoparticle synthesis and characterisation.
How the project will be supervised
This is a highly interdisciplinary project and in order to provide expertise in all areas of the project, it will involve four supervisors: Victor Chechik (nanoparticle synthesis, chemical modifications), Paul Genever (cell biology, regenerative medicine), Dani Ungar (biochemistry, ELP expression) and Gonzalo Vallejo Fernandez (magnetic properties). We have a strong track record of working together and will ensure that the student is actively interacting with at least one supervisor at all times, while having fortnightly meetings with all supervisors. You will join a vibrant, cross-departmental community of chemists and biochemists, and will have access to state-of-the-art equipment.
Training
The project will suit students interested in (bio)chemistry, biophysics, nanomaterials, drug delivery and related areas. Training in all aspects of the project will be provided. The project offers a great opportunity to consolidate ideas and expertise of different disciplines in order to develop new methodologies.
Liquids Research Limited (www.liquidsresearch.com) has provided a letter of support for the project.
Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: https://www.dimen.org.uk/blog
Further information on the programme and how to apply can be found on our website:
https://www.dimen.org.uk/how-to-apply
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