Nucleic Acid-Loaded Lipid Nanoparticle Interactions with Model Endosomal Membranes.

Content Provider	Europe PMC
Author	Spadea, Alice Jackman, Mark Cui, Lili Pereira, Sara Lawrence, M. Jayne Campbell, Richard A. Ashford, Marianne
Copyright Year	2022
Abstract	Lipid nanoparticles(LNPs) are important delivery systems for RNA-basedtherapeutics, yet the mechanism of their interaction with endosomalmembranes remains unclear. Here, the interactions of nucleic acid-loadedLNPs that contain an ionizable lipid with models of the early andlate endosomal membranes are studied, for the first time, using differentreflectometry techniques. Novel insight is provided with respect tothe subphase pH, the stage of the endosome, and the nature of thenucleic acid cargo. It is found that the insertion of lipids fromthe LNPs into the model membrane is greatest at pH 6.5 and 5.5, whereasat higher pH, lipid insertion is suppressed with evidence insteadfor the binding of intact LNPs, demonstrating the importance of thepH in the fusion of LNPs undergoing the endosomal pathway. Furthermore,and independently of the pH, the effect of the early- versus late-stageendosomal models is minimal, suggesting that the increased fluidityand anionic nature of the late endosome has little effect on the extentof LNP interaction. Last, there is greater nucleic acid delivery fromLNPs containing mRNA than Poly(A), indicating that the extent of interactioncan be tuned according to the nature of the nucleic acid cargo. Suchnew information on the relative impact of factors influencing nucleicacid delivery by LNP interactions with endosomal membranes is importantin the design and tuning of vehicles with improved nucleic acid deliverycapacities.
ISSN	19448244
Journal	ACS Applied Materials & Interfaces
Volume Number	14
PubMed Central reference number	PMC9264317
Issue Number	26
PubMed reference number	35758331
e-ISSN	19448252
DOI	10.1021/acsami.2c06065
Language	English
Publisher	American Chemical Society
Publisher Date	2022-06-27
Access Restriction	Open
Rights License	Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). © 2022 The Authors. Published by American Chemical Society
Subject Keyword	lipid nanoparticles endosomal escape Langmuirtrough ellipsometry Brewster angle microscopy(BAM)
Content Type	Text
Resource Type	Article
Subject	Nanoscience and Nanotechnology Medicine Materials Science