Evidence map›Paper›PMID 41252430›Full record

ArticleJournal of extracellular vesicles2025

Nose-to-Brain Delivery of Chlorella vulgaris Extracellular Vesicles for Antidepressant Effects.

Kangyu Jin, Ruoxi Wang, Bing Chen, Danni Zhong, Shangping Cheng, Aiying Tong, Yangjian Qi, Jing Lu, Min Zhou

Abstract read
In one paragraph

Article in Journal of extracellular vesicles, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
–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

10 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Article
  6. Engineered NestinJournal of extracellular vesicles · 2026
    Article
  7. Review
  8. Extracellular Vesicle fromInternational journal of molecular sciences · 2026
    Article
  9. Review
  10. 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

9 authors.

Kangyu JinEye Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Ruoxi WangEye Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Bing ChenDepartment of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Danni ZhongEye Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Shangping ChengInstitute of Translational Medicine, Zhejiang University, Hangzhou, China.
Aiying TongZhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University School of Medicine, Zhejiang University, Haining, China.
Yangjian QiSongjiang Research Institute, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jing LuDepartment of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Min ZhouEye Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.ORCID https://orcid.org/0000-0002-7319-9570

Funding

Binjiang Institute of Zhejiang University ZY202205SMKY007Key R&D Program of China 2022YFA1104900Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang 2022R01002National Natural Science Foundation of China 82271561National Natural Science Foundation of China 82301708Natural Science Foundation of Shandong Province ZR2023ZD30
6 · The paper itself

Abstract

Current antidepressants face limitations due to the blood-brain barrier (BBB), systemic side effects and delayed onset. Here, we engineered an intranasal thermosensitive hydrogel (EVs@IN) encapsulating Chlorella vulgaris-derived extracellular vesicles (EVs) for sustained nose-to-brain delivery. EVs@IN significantly enhanced nasal mucosal retention and facilitated targeted transport of EVs to the hippocampus via olfactory pathways, while minimizing pulmonary exposure and clearance. In mouse models of depression (LPS-induced and CUMS), intranasal EVs@IN elicited rapid and potent alleviation of depressive- and anxiety-like behaviours. Mechanistically, EVs modulated astrocyte phenotypic transformation, reducing the release of neurotoxic complement C3 and suppressing neuroinflammation. Concurrently, they activated the Nrf2-Pgc-1α pathway, enhanced antioxidant defences (elevated SOD and GSH), mitigated oxidative stress and restored synaptic plasticity and neurogenesis in the hippocampus. Furthermore, we demonstrated the capacity of EVs to serve as efficient drug carriers for brain delivery. EVs@IN exhibited excellent long-term biocompatibility in vivo. Our findings establish plant-derived EVs within a sustained-release intranasal platform as a promising, scalable and BBB-bypassing strategy for the rapid treatment of depression and potentially other neuropsychiatric disorders.

Indexed as

Antidepressive AgentsChlorella vulgarisDepressionExtracellular VesiclesAdministration, IntranasalAnimalsBlood-Brain BarrierBrainDisease Models, AnimalDrug Delivery SystemsHippocampusMaleMiceMice, Inbred C57BLNasal MucosaOxidative StressAntidepressive Agentsblood–brain barrierChlorella‐derived extracellular vesiclesintranasal administrationnose‐to‐brain pathwayrapid antidepressant

Identifiers

PMID41252430
PMCPMC12626165

What OpenQuestion holds

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LicenceCC BY
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.