Evidence map›Paper›PMID 42711375›Full record

ArticleNature nanotechnology2026

Charge-switching ionizable lipids lower the toxicity of lipid nanoparticles.

Dengpan Liang, Yalin Qi, Hesong Han, Negar Ahmadian, Kewa Gao, Kaycee Sapasap, Yuxi Zhang, Silin Guo, Atip Lawanprasert, Sopida Pimcharoen and 11 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature nanotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

21 authors.

Dengpan Liang *Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0000-0001-9898-1836
Yalin Qi *Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
Hesong Han *Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA. hanhesong@berkeley.edu.ORCID http://orcid.org/0000-0001-5545-5238
Negar Ahmadian *Department of Surgery, School of Medicine, University of California, Davis, Sacramento, CA, USA.
Kewa GaoDepartment of Surgery, School of Medicine, University of California, Davis, Sacramento, CA, USA.ORCID http://orcid.org/0000-0002-8781-890X
Kaycee SapasapInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0009-0006-2777-717X
Yuxi ZhangInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
Silin GuoInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
Atip LawanprasertInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0009-0001-3163-8803
Sopida PimcharoenDepartment of Bioengineering, Stanford University, Stanford, CA, USA.
Sheng ZhaoInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
Milan T Del BuonoInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
He XiaDepartment of Surgery, School of Medicine, University of California, Davis, Sacramento, CA, USA.
Zoe O EndersDepartment of Surgery, School of Medicine, University of California, Davis, Sacramento, CA, USA.ORCID http://orcid.org/0009-0007-3754-7826
Benjamin W BurgstoneInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.ORCID http://orcid.org/0009-0000-8256-3867
Antonino CalioMolecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, CA, USA.ORCID http://orcid.org/0000-0003-2324-2902
Neel DankarInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
Bingwei LuDepartment of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
Lei S QiDepartment of Bioengineering, Stanford University, Stanford, CA, USA.
Aijun WangDepartment of Surgery, School of Medicine, University of California, Davis, Sacramento, CA, USA. aawang@health.ucdavis.edu.ORCID http://orcid.org/0000-0002-2985-3627
Niren MurthyInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA. nmurthy@berkeley.edu.ORCID http://orcid.org/0000-0002-7815-7337

Funding

California Institute for Regenerative Medicine (CIRM) DISC2-14045California Institute for Regenerative Medicine (CIRM) DISC2-14097
6 · The paper itself

Abstract

Lipid nanoparticles (LNPs) have great potential as nucleic acid delivery vehicles; however, they trigger the production of inflammatory cytokines, which limits their medical applications. Developing non-inflammatory LNPs is challenging because the LNP's ionizable lipid and the process of endosomal disruption are the major sources of LNP toxicity but are also essential for delivering nucleic acids. Here we demonstrate that ionizable lipids containing a carboxylic acid and an amine (termed S-lipid) switch their charged state between the pHs of 7.4 and 4.0, allowing them to generate LNPs (termed switchable nanoparticles) that efficiently encapsulate nucleic acid and trigger endosomal release without activation of the TLR4, complement, galectin-8 and platelet activating factor signalling pathways. Finally, we demonstrate that switchable nanoparticles are better at treating lipopolysaccharide-induced acute lung injury than traditional LNPs because they do not exacerbate pre-existing inflammation. Collectively, these results demonstrate that negatively charged ionizable lipids can mitigate the toxicity of LNPs.

Identifiers

PMID42711375

What OpenQuestion holds

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Registered trials

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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.