Evidence map›Paper›PMID 40074542›Full record

ArticleACS nano2025

Buffer Specificity of Ionizable Lipid Nanoparticle Transfection Efficiency and Bulk Phase Transition.

Cristina Carucci, Julian Philipp, Judith A Müller, Akhil Sudarsan, Ekaterina Kostyurina, Clement E Blanchet, Nadine Schwierz, Drew F Parsons, Andrea Salis, Joachim O Rädler

Abstract read
In one paragraph

Article in ACS nano, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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

7 citing papers in PubMed.

  1. Review
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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

10 authors.

Cristina CarucciDepartment of Chemical and Geological Sciences, University of Cagliari & Center for Colloid and Surface Science (CSGI), Cittadella Universitaria, 09042 Monserrato, CA, Italy.ORCID 0000-0001-8660-788X
Julian PhilippFaculty of Physics, Ludwig-Maximilians University, Geschwister-Scholl-Platz 1, 80539 Munich, Germany.
Judith A MüllerFaculty of Physics, Ludwig-Maximilians University, Geschwister-Scholl-Platz 1, 80539 Munich, Germany.ORCID 0000-0001-6312-4893
Akhil SudarsanInstitute of Physics, University of Augsburg, 86159 Augsburg, Germany.ORCID 0009-0004-5910-4709
Ekaterina KostyurinaFaculty of Physics, Ludwig-Maximilians University, Geschwister-Scholl-Platz 1, 80539 Munich, Germany.
Clement E BlanchetEuropean Molecular Biology Laboratory Hamburg Outstation c/o Deutsches Elektronen-Synchrotron, 22607 Hamburg, Germany.
Nadine SchwierzInstitute of Physics, University of Augsburg, 86159 Augsburg, Germany.
Drew F ParsonsDepartment of Chemical and Geological Sciences, University of Cagliari & Center for Colloid and Surface Science (CSGI), Cittadella Universitaria, 09042 Monserrato, CA, Italy.ORCID 0000-0002-3956-6031
Andrea SalisDepartment of Chemical and Geological Sciences, University of Cagliari & Center for Colloid and Surface Science (CSGI), Cittadella Universitaria, 09042 Monserrato, CA, Italy.ORCID 0000-0001-5746-2693
Joachim O RädlerFaculty of Physics, Ludwig-Maximilians University, Geschwister-Scholl-Platz 1, 80539 Munich, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lipid nanoparticles (LNPs) are efficient and safe carriers for mRNA vaccines based on advanced ionizable lipids. It is understood that the pH-dependent structural transition of the mesoscopic LNP core phase plays a key role in mRNA transfer. However, buffer-specific variations in transfection efficiency remain obscure. Here we analyze the effect of the buffer type on the transfection efficiency of LNPs. We find that LNPs formulated with the cationic ionizable lipids DLin-MC3-DMA (MC3), SM-102, and ALC-315 in citrate compared to phosphate and acetate buffers exhibit earlier onset and stronger mRNA-GFP expression in vitro. Using synchrotron small-angle X-ray scattering (SAXS) we determine the buffer specificity of the pH-dependent structure of ionizable lipid/cholesterol/water mesophases that serve as model systems for the LNP core phase. The results show that the phase transition from inverse micellar to inverse hexagonal with decreasing pH is shifted to a lower transition pH for acetate and phosphate compared with citrate buffer. Based on continuum theory and ion-specific adsorption obtained from all-atom MD simulations, we propose a mechanism for buffer specificity. Citrate stabilizes the inverse hexagonal phase thus shifting the formation of H

Indexed as

LipidsNanoparticlesTransfectionBuffersHumansHydrogen-Ion ConcentrationPhase TransitionRNA, MessengerBuffersLipidsRNA, MessengerDLin-MC3-DMAionizable lipidslipid nanoparticlespH transitionspecific buffer effectstransfection efficiency

Identifiers

PMID40074542
PMCPMC11949115

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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 OpenQuestion graph.