Evidence map›Paper›PMID 35758331›Full record

ArticleACS applied materials & interfaces2022

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

Alice Spadea, Mark Jackman, Lili Cui, Sara Pereira, M Jayne Lawrence, Richard A Campbell, Marianne Ashford

Open access · hybridAbstract read
In one paragraph

Article in ACS applied materials & interfaces, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
4.1field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 51 citations in OpenAlex.

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  14. Endosomal escape: A bottleneck for LNP-mediated therapeutics.Proceedings of the National Academy of Sciences of the United States of America · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 3 countries.

Alice SpadeaNorthWest Centre for Advanced Drug Delivery (NoWCADD), School of Health Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, U.K.ORCID 0000-0002-8857-330X
Mark JackmanAdvanced Drug Delivery, Pharmaceutical Sciences, AstraZeneca R&D, Cambridge CB2 0AA, U.K.ORCID 0000-0002-0479-1079
Lili CuiAdvanced Drug Delivery, Pharmaceutical Sciences, AstraZeneca R&D, Cambridge CB2 0AA, U.K.ORCID 0000-0002-0668-2837
Sara PereiraAdvanced Drug Delivery, Pharmaceutical Sciences, AstraZeneca R&D, Cambridge CB2 0AA, U.K.
M Jayne LawrenceNorthWest Centre for Advanced Drug Delivery (NoWCADD), School of Health Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, U.K.ORCID 0000-0003-4738-4841
Richard A CampbellDivision of Pharmacy and Optometry, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PT, U.K.ORCID 0000-0002-6296-314X
Marianne AshfordAdvanced Drug Delivery, Pharmaceutical Sciences, AstraZeneca R&D, Macclesfield SK10 2NA, U.K.ORCID 0000-0002-8390-4800
AstraZeneca (United Kingdom) · GBUniversity of Manchester · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lipid nanoparticles (LNPs) are important delivery systems for RNA-based therapeutics, yet the mechanism of their interaction with endosomal membranes remains unclear. Here, the interactions of nucleic acid-loaded LNPs that contain an ionizable lipid with models of the early and late endosomal membranes are studied, for the first time, using different reflectometry techniques. Novel insight is provided with respect to the subphase pH, the stage of the endosome, and the nature of the nucleic acid cargo. It is found that the insertion of lipids from the LNPs into the model membrane is greatest at pH 6.5 and 5.5, whereas at higher pH, lipid insertion is suppressed with evidence instead for the binding of intact LNPs, demonstrating the importance of the pH in the fusion of LNPs undergoing the endosomal pathway. Furthermore, and independently of the pH, the effect of the early- versus late-stage endosomal models is minimal, suggesting that the increased fluidity and anionic nature of the late endosome has little effect on the extent of LNP interaction. Last, there is greater nucleic acid delivery from LNPs containing mRNA than Poly(A), indicating that the extent of interaction can be tuned according to the nature of the nucleic acid cargo. Such new information on the relative impact of factors influencing nucleic acid delivery by LNP interactions with endosomal membranes is important in the design and tuning of vehicles with improved nucleic acid delivery capacities.

Indexed as

LipidsNanoparticlesEndosomesLiposomesRNA, MessengerRNA, Small InterferingLipid NanoparticlesLipidsLiposomesRNA, MessengerRNA, Small InterferingBrewster angle microscopy (BAM)ellipsometryendosomal escapeLangmuir troughlipid nanoparticles

Identifiers

PMID35758331
PMCPMC9264317
OpenAlexW4283579582

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.