Leiden University Scholarly Publications

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Papadopoulou, P. (2023)

Phase separation in lipid-based nanoparticles: exploring the nano-bio interface

Doctoral Thesis
This doctoral thesis is an effort to understand how lipid phase-separation induced by diacylglycerol analogues in lipid-based nanoparticles affects their in vivo behavior, leading to specific nanoparticle-protein communications and selective cell targeting. By studying how lipid composition affects morphology and this in turn affects the nano-bio interface, a comprehensive picture and prediction of nanoparticle behavior and cell selectivity is provided. More specifically, liposomes containing diacylglycerol analogues are found to phase separate and to be able to specifically target subsets of endothelial cells in zebrafish embryos. The mechanism behind this selective targeting is the result of a triglyceride lipase mediated mechanism due to phase separation and lipid composition, and is conserved in higher organisms (mice). Moreover, mRNA-based lipid nanoparticles that contain diacylglycerol analogues exhibit the same selectivity which leads to cell-specific mRNA delivery and...Show moreThis doctoral thesis is an effort to understand how lipid phase-separation induced by diacylglycerol analogues in lipid-based nanoparticles affects their in vivo behavior, leading to specific nanoparticle-protein communications and selective cell targeting. By studying how lipid composition affects morphology and this in turn affects the nano-bio interface, a comprehensive picture and prediction of nanoparticle behavior and cell selectivity is provided. More specifically, liposomes containing diacylglycerol analogues are found to phase separate and to be able to specifically target subsets of endothelial cells in zebrafish embryos. The mechanism behind this selective targeting is the result of a triglyceride lipase mediated mechanism due to phase separation and lipid composition, and is conserved in higher organisms (mice). Moreover, mRNA-based lipid nanoparticles that contain diacylglycerol analogues exhibit the same selectivity which leads to cell-specific mRNA delivery and transfection.
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Nanomedicine
Lipid-based nanoparticles
Phase separation
Cryo-electron microscopy
Nano-bio interface
Zebrafish
mRNA-LNPs
All authors
Papadopoulou, P.
Supervisor
Kros, A.
Co-supervisor
Noort, J.S.T. van
Committee
Ubbink, M.; Bonnet, S.; Akkari, L.; Sommerdijk, N.A.J.M.; Sharp, T.H.
Qualification
Doctor (dr.)
Awarding Institution
Leiden Institute of Chemistry (LIC), Faculty of Science, Leiden University
Date
2023-11-07