Interaction Kinetics of Individual mRNA-Containing Lipid Nanoparticles with an Endosomal Membrane Mimic: Dependence on pH, Protein Corona Formation, and Lipoprotein Depletion | Sciact - CRIS-system of Boreskov Institute of Catalysis

Interaction Kinetics of Individual mRNA-Containing Lipid Nanoparticles with an Endosomal Membrane Mimic: Dependence on pH, Protein Corona Formation, and Lipoprotein Depletion Full article

Journal

ACS Nano
ISSN: 1936-0851 , E-ISSN: 1936-086X

Output data

Year: 2022, Volume: 16, Number: 12, Pages: 20163–20173 Pages count : 11 DOI: 10.1021/acsnano.2c04829

Tags

endosomal membrane; ionizable lipid nanoparticle; lipoprotein; mRNA delivery; protein corona

Authors

Aliakbarinodehi Nima ¹ , Gallud Audrey ^2,3 , Mapar Mokhtar ¹ , Wesén Emelie ² , Heydari Sahar ² , Jing Yujia ³ , Emilsson Gustav ³ , Liu Kai ³ , Sabirsh Alan ³ , Zhdanov Vladimir P. ^1,4 , Lindfors L.Lennart ³ , Esbjörner E.K. ² , Höök Fredrik ¹

Affiliations

1	Division of Nano and Biophysics, Department of Physics, Chalmers University of Technology, 41296 Göteborg, Sweden
2	Division of Chemical Biology, Department of Biology and Biological Engineering, Chalmers University of Technology, 41296 Göteborg, Sweden
3	Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, 43181 Gothenburg, Sweden
4	Boreskov Institute of Catalysis, Russian Academy of Sciences, Novosibirsk 630090, Russia

Funding (1)

Stiftelsen för strategisk forskning

IRC15-0065

Lipid nanoparticles (LNPs) have emerged as potent carriers for mRNA delivery, but several challenges remain before this approach can offer broad clinical translation of mRNA therapeutics. To improve their efficacy, a better understanding is required regarding how LNPs are trapped and processed at the anionic endosomal membrane prior to mRNA release. We used surface-sensitive fluorescence microscopy with single LNP resolution to investigate the pH dependency of the binding kinetics of ionizable lipid-containing LNPs to a supported endosomal model membrane. A sharp increase of LNP binding was observed when the pH was lowered from 6 to 5, accompanied by stepwise large-scale LNP disintegration. For LNPs preincubated in serum, protein corona formation shifted the onset of LNP binding and subsequent disintegration to lower pH, an effect that was less pronounced for lipoprotein-depleted serum. The LNP binding to the endosomal membrane mimic was observed to eventually become severely limited by suppression of the driving force for the formation of multivalent bonds during LNP attachment or, more specifically, by charge neutralization of anionic lipids in the model membrane due to their association with cationic lipids from earlier attached LNPs upon their disintegration. Cell uptake experiments demonstrated marginal differences in LNP uptake in untreated and lipoprotein-depleted serum, whereas lipoprotein-depleted serum increased mRNA-controlled protein (eGFP) production substantially. This complies with model membrane data and suggests that protein corona formation on the surface of the LNPs influences the nature of the interaction between LNPs and endosomal membranes. © 2022 The Authors. Published by American Chemical Society.

Aliakbarinodehi N. , Gallud A. , Mapar M. , Wesén E. , Heydari S. , Jing Y. , Emilsson G. , Liu K. , Sabirsh A. , Zhdanov V.P. , Lindfors L.L. , Esbjörner E.K. , Höök F.
Interaction Kinetics of Individual mRNA-Containing Lipid Nanoparticles with an Endosomal Membrane Mimic: Dependence on pH, Protein Corona Formation, and Lipoprotein Depletion
ACS Nano. 2022. V.16. N12. P.20163–20173. DOI: 10.1021/acsnano.2c04829 WOS Scopus РИНЦ ANCAN PMID OpenAlex

Submitted:	May 17, 2022
Accepted:	Dec 6, 2022
Published online:	Dec 13, 2022
Published print:	Dec 27, 2022

Web of science:	WOS:000897267300001
Scopus:	2-s2.0-85144101490
Elibrary:	54734450
Chemical Abstracts:	2022:3079851
Chemical Abstracts (print):	181:109002
PMID:	36511601
OpenAlex:	W4311282977

DB	Citing
Scopus	41
Web of science	41
OpenAlex	43
Elibrary	33