Polymer-engineering nanocages for protein delivery

About the Project

Protein therapeutics are a fast-acting and potent class of medicine with remarkable success in the treatment of several relevant disorders. Despite significant advantages, therapeutic safety and efficacy are hampered by protein instability, short circulation half-life and immunogenicity. Nanocarriers have found clinical success in macromolecular delivery by improving pharmacokinetic properties, facilitating cellular internalisation, and enhancing target affinity. However, therapeutic outcomes are often challenged by low protein encapsulation. Ideal protein-loaded nanocarriers must be able to carry high cargo doses for efficient therapy.

The proposed PhD project will focus on developing ferritin nanocages for protein delivery. Ferritin is a natural nanocarrier with high structural stability, biocompatibility, and biodegradability. Self-assembled from multiple protein subunits, ferritin forms a hollow cavity that can accommodate protein cargo and three distinct surfaces (external, interior, and inter-subunit) that can be functionalised to create a powerful ‘smart’ delivery platform. Protein encapsulation is dependent on the electrostatic interactions during ferritin self-assembly. The scientific approach of this project is thus to increase the attractive interactions between the interior surface microenvironment and the protein cargo to enhance encapsulation and stability. To do so, charged and/or stimuli-responsive polymers will be used to re-engineer the ferritin microenvironment. Ferritin-polymer conjugates will be characterised and impact of the inner surface charge on protein encapsulation as a function of pH and ionic strength investigated using protein cargos with varied size and surface charge. Findings from this project will lead towards temporal and distribution-controlled protein release and targeted therapy. The successful candidate will be part of a highly interdisciplinary project and have the opportunity to learn about polymer synthesis, bioconjugation, protein formulation and characterisation, and biological testing.

Training will be provided in a range of techniques including polymer synthesis bioconjugation, protein-polymer purification and characterisation and performance characterisation including in vitro bioactivity, drug release and stability assays. The student will also develop generic research skills in scientific writing, literature reviewing, time management and delivery of presentations, nationally and internationally.

The PhD student will be encouraged to engage in a variety of impact activities, disseminate the research project findings through publications, public talks, and participate in QUB showcase events.

Funding Notes

This project is not funded; applications are welcome from self-funding candidates.