Evidence map›Paper›PMID 39300226›Full record

ArticleNature nanotechnology2024

Direct cytosolic delivery of siRNA via cell membrane fusion using cholesterol-enriched exosomes.

Yan Zhuo, Zhen Luo, Zhu Zhu, Jie Wang, Xiang Li, Zhuan Zhang, Cong Guo, Bingqi Wang, Di Nie, Yong Gan and 2 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature nanotechnology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.

0numbers the graph read from it
0cells of the map it votes in
80citing 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

80 citing papers in PubMed.

  1. Article
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  9. Exosome-mediated siRNA delivery in cancer: Loading strategies, targeting approaches, and therapeutic outcomes.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026
    Review
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20 more citing papers are in PubMed but not listed here.

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

12 authors.

Yan Zhuo *State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Zhen Luo *Department of Engineering Mechanics, State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University, Hangzhou, China.
Zhu ZhuState Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0009-0000-2337-8434
Jie WangState Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Xiang LiState Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0009-0000-9342-5806
Zhuan ZhangState Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0009-0007-7648-4936
Cong GuoState Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Bingqi WangState Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Di NieState Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Yong GanState Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. ygan@simm.ac.cn.ORCID http://orcid.org/0000-0002-4579-994X
Guoqing HuDepartment of Engineering Mechanics, State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University, Hangzhou, China. ghu@zju.edu.cn.ORCID http://orcid.org/0000-0001-9451-5336
Miaorong YuState Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. mryu@simm.ac.cn.ORCID http://orcid.org/0000-0002-0474-5339

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82073773
6 · The paper itself

Abstract

Efficient cytosolic delivery is a significant hurdle when using short interfering RNA (siRNA) in therapeutic applications. Here we show that cholesterol-rich exosomes are prone to entering cancer cells through membrane fusion, achieving direct cytosolic delivery of siRNA. Molecular dynamics simulations suggest that deformation and increased contact with the target cell membrane facilitate membrane fusion. In vitro we show that cholesterol-enriched milk-derived exosomes (MEs) achieve a significantly higher gene silencing effect of siRNA, inducing superior cancer cell apoptosis compared with the native and cholesterol-depleted MEs, as well as conventional transfection agents. When administered orally or intravenously to mice bearing orthotopic or subcutaneous tumours, the cholesterol-enriched MEs/siRNA exhibit antitumour activity superior to that of lipid nanoparticles. Collectively, by modulating the cholesterol content of exosome membranes to facilitate cell entry via membrane fusion, we provide a promising approach for siRNA-based gene therapy, paving the way for effective, safe and simple gene therapy strategies.

Indexed as

CholesterolCytosolExosomesMembrane FusionRNA, Small InterferingAnimalsApoptosisCell Line, TumorHumansMiceCholesterolRNA, Small Interfering

Identifiers

PMID39300226

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.