Lipid nanoparticles-Apolipoprotein E interaction: the role of LNPs surface composition and structure
Therapeutic treatments based on the production of proteins by delivering messenger RNA (mRNA) represent a promising approach. One of the major challenges is to protect mRNA from enzymatic degradation and deliver it into the target cells. Lipid nanoparticles (LNPs) formed by a cationic ionizable lipid (CIL), DSPC, cholesterol and a pegylated lipid have been successful to deliver small interference RNA. Physical and chemical characterization of these LNPs is needed to progress from pre-clinical testing. 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. Apolipoprotein E (ApoE). ApoE, being responsible for fat transport in the body, 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 investigate the role of LNP surface structure on the ApoE binding and the structural change, in particular at the surface, due to ApoE binding.
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SEBASTIANI Federica; CARDENAS; PORCAR Lionel; Sarah Waldie and Marianna Yanez Arteta. (2019). Lipid nanoparticles-Apolipoprotein E interaction: the role of LNPs surface composition and structure. Institut Laue-Langevin (ILL) doi:10.5291/ILL-DATA.9-13-866
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