Evidence map›Paper›PMID 40846096›Full record

ArticleActa biomaterialia2025

Sulfonium lipid nanoparticles for intranasal mRNA delivery to lung epithelial and immune cells.

Yuqin Men, David O Popoola, Zhi Cao, Yiran Li, Stephan Wilkens, Yong Teng, Qinghe Meng, Marc Hershenson, Yamin Li

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta biomaterialia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
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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

9 authors.

Yuqin MenDepartment of Pharmacology, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA.
David O PopoolaDepartment of Pharmacology, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA.
Zhi CaoDepartment of Pharmacology, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA.
Yiran LiDepartment of Pediatrics, Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Stephan WilkensDepartment of Biochemistry and Molecular Biology, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA.
Yong TengDepartment of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
Qinghe MengDepartment of Surgery, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA; Sepsis Interdisciplinary Research Center (SIRC), State University of New York, Upstate Medical University, Syracuse, NY 13210, USA.
Marc HershensonDepartment of Pediatrics, Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Yamin LiDepartment of Pharmacology, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA; Sepsis Interdisciplinary Research Center (SIRC), State University of New York, Upstate Medical University, Syracuse, NY 13210, USA. Electronic address: liyam@upstate.edu.

Funding

Early Life Rhinovirus Infection and Childhood AsthmaR01AI120526 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HERSHENSON, MARC B. · 2016 to 2024
$3.9M
Models of rhinovirus-C respiratory infection and asthmaR01AI155444 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HERSHENSON, MARC B. · 2020 to 2024
$2.1M
Structure and Regulatory Mechanisms of the Vacuolar ATPaseR35GM141908 · NIGMS · UPSTATE MEDICAL UNIVERSITY · PI WILKENS, STEPHAN · 2021 to 2025
$2.1M
Developing sulfonium lipid nanoparticles as a novel platform for mRNA deliveryR35GM160083 · NIGMS · UPSTATE MEDICAL UNIVERSITY · PI Yamin Li · 2025 to 2026
$897k
Early Life Rhinovirus Infection and Childhood AsthmaR56AI120526 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HERSHENSON, MARC B. · 2015 to 2015
$439k
Development of Sulfonium- and Phosphonium-based Cationic Lipid Materials for mRNA DeliveryR03EB032579 · NIBIB · UPSTATE MEDICAL UNIVERSITY · PI LI, YAMIN · 2022 to 2023
$163k
NIAID NIH HHS R01 AI120526NIAID NIH HHS R01 AI155444NIAID NIH HHS R56 AI120526NIBIB NIH HHS R03 EB032579NIGMS NIH HHS R35 GM141908NIGMS NIH HHS R35 GM160083
6 · The paper itself

Abstract

Lung epithelial and immune cells play an important role in respiratory health, serving as the first line of defense. Targeting these cells presents significant therapeutic opportunities, particularly for mRNA-based medicine. However, efficient mRNA delivery to lung cells remains challenging due to mucosal barriers, enzymatic degradation, and complex tissue architecture. In this study, we developed sulfonium lipid nanoparticles (sLNPs) featuring a sulfonium head group and branched tail structure. These sLNPs efficiently delivered mRNA to lung epithelial and immune cells via intranasal instillation in mice, transfecting club cells, ciliated cells, and macrophages, which are key players in lung structure and function. Additionally, sLNPs successfully delivered CRISPR-Cas9 mRNA and sgRNA for genome editing, as well as cytokine mRNA for immune modulation in the lungs. The sLNP platform demonstrated safety in adult mice, with no significant local or systemic tissue damage observed. These findings highlight the sLNP platform's effectiveness and versatility in delivering diverse mRNA molecules, demonstrating its potential for applications ranging from gene editing to immunomodulation therapies. With further optimization, the sLNP system could pave the way for advanced mRNA-based treatments for lung diseases. STATEMENT OF SIGNIFICANCE: Almost all of the previously developed lipids for pulmonary mRNA delivery are amine-based. We designed and synthesized a group of lipids featuring the sulfonium charge-carrying group for mRNA delivery. This is the first demonstration of employing sulfonium lipid nanoparticles (sLNPs) for mRNA delivery to lung epithelial and immune cells in vivo. These sLNPs enabled efficient pulmonary delivery of diverse mRNA cargos, supporting applications such as bioluminescence imaging, gene editing, and immunomodulation. Club and ciliated cells as well as macrophages in the bronchoalveolar fluid, were successfully transfected. No sustained inflammation or toxicity was induced, highlighting the safety of these sulfonium lipid materials.

Indexed as

Epithelial CellsGene Transfer TechniquesLipidsLungMacrophagesNanoparticlesRNA, MessengerSulfonium CompoundsAdministration, IntranasalAnimalsHumansLiposomesMiceMice, Inbred C57BLLipid NanoparticlesLipidsLiposomesRNA, MessengerSulfonium CompoundsGene editingLipid nanoparticleLung-targetingmRNA deliverySulfonium lipid

Identifiers

PMID40846096
PMCPMC13179572

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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.