Lipid nanoparticles-Apolipoprotein E interaction: the role of LNP surface composition and structure

Therapeutic treatments based on the production of proteins by delivering messenger RNA (mRNA) represent a promising approach. Lipid nanoparticles (LNPs) formed by a cationic ionizable lipid (CIL), DSPC, cholesterol and a pegylated lipid have been successful to deliver small interference RNA. The bio-distribution and cellular uptake of LNPs are affected by their surface composition as well as by the extracellular proteins present at the site of LNPs administration, e.g. ApolipoproteinE (ApoE). ApoE plays a key role in the LNP’s circulation time. Our previous results show that both particle size and DSPC surface area affects the efficacy of LNPs. For an optimised LNP formulation, we aim to reveal the contribution of CIL and cholesterol to the LNP structure. Furthermore, we want to study the role of LNP surface structure on the ApoE binding and the structural change due to ApoE binding.