Engineering the Protein Corona: Characterisation of LNP-BSA Complexes for Enhanced Drug Delivery and Therapeutic Efficacy

Following their success as mRNA vaccine carriers during the COVID-19 pandemic, lipid nanoparticles (LNPs) have gained recognition as promising drug delivery systems. However, challenges persist, particularly due to the formation of a protein corona (PC) when LNPs are exposed to serum proteins, which can alter their biodistribution and therapeutic outcomes. Proteins such as bovine serum albumin (BSA) have demonstrated synergistic effects in enhancing LNP delivery, but the interaction between LNPs and serum proteins is complex, influenced by individual genetic and environmental factors. Thus, this proposal aims to use SANS to investigate the interaction between LNPs and BSA and explore the feasibility of engineering the PC by covalently pre-coating LNPs with BSA to form stable and standardised LNP-PC complexes. Using an LNP-protein separation method developed during our previous beamtime, we can remove unabsorbed proteins and obtain clear scattering data. This structural information will be integrated into our multi-scale LNP characterisation pipeline, offering a comprehensive model of LNP-BSA complexes, including correlations with physiological properties, composition, nanostructure and physiological behaviours. Ultimately, this study will provide new insights into LNP-protein interactions and present a novel method to control LNP-PC formation, which could lead to more robust and predictable therapeutic outcomes and support advancements in personalised medicine.