Evidence map›Paper›PMID 40659631›Full record

ArticleNature communications2025

Boosting RNA nanotherapeutics with V-ATPase activating non-inflammatory lipid nanoparticles to treat chronic lung injury.

Zhiqiang Zhao, Xinzhu Shan, Jing Ding, Bin Ma, Buyao Li, Wendi Huang, Qingqing Yang, Yian Fang, Junhe Chen, Chenglin Song and 12 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

  1. Review
  2. Bioactive lipid-derived nanoparticles for RNA delivery.Materials today (Kidlington, England) · 2026
    Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Decoding Undesirable Inflammatory Responses of Nucleic Acid-Delivering Lipid Nanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Advances in Inhaled Nanoparticle Drug Delivery for Pulmonary Disease Management.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Review
  17. Review
  18. Review
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

22 authors.

Zhiqiang Zhao *State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Xinzhu Shan *State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Jing Ding *Department of Pediatrics, Peking University People's Hospital, Beijing, PR China. dingjingvv@126.com.ORCID http://orcid.org/0009-0003-3667-3194
Bin Ma *State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Buyao LiState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Wendi HuangShanghai Institute for Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.
Qingqing YangPeking University International Cancer Institute, Beijing, China.
Yian FangState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Junhe ChenUniversity of North Carolina at Chapel Hill, North Carolina, USA.
Chenglin SongState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Chenlong WeiState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Shuai LiuBeijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Colloid, Interface and Chemical Thermodynamics, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China.
Xingdi ChengBeijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Colloid, Interface and Chemical Thermodynamics, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China.
Shengran ZhangState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Yunxuan LiuState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Hongkun WuDepartment of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.ORCID http://orcid.org/0000-0002-9459-6583
Cong LuoDepartment of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, China.ORCID http://orcid.org/0000-0002-0506-9598
Shaokun ShuPeking University International Cancer Institute, Beijing, China.ORCID http://orcid.org/0000-0001-6839-2782
Xue QiaoState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.ORCID http://orcid.org/0000-0002-8771-7877
Zefeng WangShanghai Institute for Nutrition and Health, Chinese Academy of Sciences, Shanghai, China. wangzf@sustech.edu.cn.ORCID http://orcid.org/0000-0002-6605-3637
Xueguang LuBeijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Colloid, Interface and Chemical Thermodynamics, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China. xueguang@iccas.ac.cn.ORCID http://orcid.org/0000-0002-1069-7265
Lei MiaoState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China. lmiao_pharm@bjmu.edu.cn.ORCID http://orcid.org/0009-0004-1647-1445

Funding

Beijing Municipal Science and Technology Commission Z231100007223012National Natural Science Foundation of China (National Science Foundation of China) 82373807, 82070460, 82270479, 32030064, 32250013, 22175188Natural Science Foundation of Beijing Municipality (Beijing Natural Science Foundation) Z220022
6 · The paper itself

Abstract

Lipid nanoparticles (LNPs) are a promising platform for mRNA delivery. However, their use in inflammatory pulmonary diseases is limited by reactogenicity and suboptimal delivery. Here we develop a non-inflammatory LNP (NIF-LNP) by incorporating ursolic acid, identified from a natural product library, into a biodegradable, cationic phosphoramide-derived LNP formulation. NIF-LNPs exhibit a 40-fold enhancement in lung protein expression without causing significant reactogenicity compared to LNPs containing ALC-0315. Our CRISPR-KO mechanistic studies uncover that ursolic acid promote endosome acidification by activating the V-ATPase complex, acting as a central hub for endosomal trafficking of LNPs and inflammation control. Furthermore, we identify an intracellular circadian regulatory gene, NR1D1, encapsulated in NIF-LNPs, showing notable therapeutic efficacy in bronchopulmonary dysplasia and lung fibrosis. To enhance clinical feasibility, we have developed a lyophilized formulation that maintains stability for over 90 days and ensures efficient nebulization in preclinical male mouse, pup rat, and male dog models. Overall, this V-ATPase-activating atomized NIF-LNP presents a viable strategy for treating variable chronic inflammatory lung diseases.

Indexed as

Lung InjuryNanoparticlesRNAVacuolar Proton-Translocating ATPasesAnimalsDisease Models, AnimalDogsHumansLipidsLiposomesLungMaleMiceRatsLipid NanoparticlesLipidsLiposomesRNAVacuolar Proton-Translocating ATPases

Identifiers

PMID40659631
PMCPMC12259844

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.