The tiny fatty particles that made mRNA COVID-19 vaccines work are getting a redesign to fix two stubborn problems: they provoke unwanted immune reactions and fall apart if not kept frozen. These particles, called lipid nanoparticles (LNPs), are coated with polyethylene glycol (PEG), a polymer that stabilises them. But PEG can trigger the immune system, and the particles degrade at room temperature. This research swaps PEG for an alternative called polysarcosine (pSar) and tweaks the particle size and composition to find a combination that delivers its payload without provoking the body or spoiling on the shelf. If successful, the work could produce vaccines and therapeutics that survive standard refrigeration—or even room temperature—rather than requiring deep-freeze supply chains. That would make mRNA-based medicines practical for developing nations, where cold storage is often unavailable. The team at Nottingham is using a technique called OrbiSIMS to measure how individual immune cells take up these particles and respond, using only tens of cells instead of hundreds of thousands. Machine-learning collaborators at Seikei University in Japan will help interpret the resulting data to link particle chemistry to cellular behaviour. The outcome is a faster, cheaper way to test many LNP formulations at once, accelerating the development of stable, effective delivery systems for vaccines and gene therapies.
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This research project aims to develop advanced healthcare materials in the form of novel lipid nanoparticles (LNPs) for applications in vaccines and wider therapeutics. Although successfully developed for COVID-19 vaccines, LNPs have great potential for improvement, specifically with regards to their interaction with the immune system as well as storage stability. This project aims to optimise an existing polyethylene glycol (PEG) based LNP system, modifying PEG composition and exploring a recently proposed alternative to PEG to enable an appropriate immune response and improved storage stability. Improved storage will help to tackle inequalities faced by developing nations where LNPs cannot be effectively distributed worldwide. Our innovative approach utilises recent methodology advances by our research team at Nottingham using OrbiSIMS analysis to simultaneously study LNP uptake in immune cells and the associated immune responses. This approach is high throughput and cost effective compared to existing as it can assess LNP uptake and cellular response simultaneously throughout a broad range of chemistries using very low cell numbers (tens of cells as opposed to hundreds of thousands). The OrbiSIMS data-sets generated with this new protocol are vast and complex and so in order to ensure they are fully utilised this research project will further expand an existing collaboration with experts in machine learning at Seikei University (Japan). This analysis will enable a correlation to be made between the LNP modifications and cellular uptake and metabolomic response. Our research will enable a new understanding in the impact of parameters such as LNP size, PEG molecular weight, concentration and the impact using the PEG alternative, polysarcosine (pSar). The ability to tailor these aspects will allow LNPs to be developed which can maximise delivery, immune response, transfection efficiency and storage stability. The interdisciplinary team combines unique experimental and data-processing capability and expertise from the UK and Japan and is well-positioned to drive innovation in LNP technology. This international research collaboration will have global reach advancing areas of vaccine and therapeutic delivery, contributing to the development of more efficacious and stable healthcare materials for vaccine and therapeutic delivery. This work aligns with UKRI EPSRC's priorities impacting multiple research themes, including physical sciences and healthcare technologies. Benefits will be realised in numerous fields such as medicine, materials science, biotechnology, biology and pharmaceutics. The research supports the UKRI's strategic theme of 'Securing better health, ageing, and wellbeing' and the United Nations Goal to 'Ensure healthy lives and promote well-being for all at all ages' amongst others. This research will establish a novel high throughput approach to developing advanced healthcare materials.
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