Evidence map›Paper›PMID 41083985›Full record

ArticleJournal of nanobiotechnology2025

Biomimetic ferritin nanocages for synergistic co-delivery of metformin and rapamycin restore neurodevelopmental homeostasis in autism spectrum disorders.

Yizhe Shen, Lele Yu, Liujiao Wang, Jilu Jin, Cheng Yu, Yuan Fan, Yue Lang, Huashan Xu, Byron C Jones, Yishi Liu and 4 more

Abstract read
In one paragraph

Article in Journal of nanobiotechnology, 2025. 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. 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

14 authors.

Yizhe Shen *School of Life Sciences, Shanghai University, 99 Shangda Road, Shanghai China, 200444, P. R. China.
Lele Yu *School of Environmental and Chemical Engineering, Shanghai University, 99 Shangda Road, Shanghai China, 200444, P. R. China.
Liujiao WangSchool of Life Sciences, Shanghai University, 99 Shangda Road, Shanghai China, 200444, P. R. China.
Jilu JinSchool of Life Sciences, Shanghai University, 99 Shangda Road, Shanghai China, 200444, P. R. China.
Cheng YuKey Laboratory of Carbohydrate Chemistry and Biotechnology, School of Biotechnology, Ministry of Education, Jiangnan University, Wuxi, 214122, Jiangsu, China.
Yuan FanSchool of Environmental and Chemical Engineering, Shanghai University, 99 Shangda Road, Shanghai China, 200444, P. R. China.
Yue LangSchool of Life Sciences, Shanghai University, 99 Shangda Road, Shanghai China, 200444, P. R. China.
Huashan XuSchool of Life Sciences, Shanghai University, 99 Shangda Road, Shanghai China, 200444, P. R. China.
Byron C JonesDepartment of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, USA.
Yishi LiuKey Laboratory of Carbohydrate Chemistry and Biotechnology, School of Biotechnology, Ministry of Education, Jiangnan University, Wuxi, 214122, Jiangsu, China.
Jiaying WuSchool of Life Sciences, Shanghai University, 99 Shangda Road, Shanghai China, 200444, P. R. China.
Siyuan GaoSchool of Life Sciences, Shanghai University, 99 Shangda Road, Shanghai China, 200444, P. R. China.
Fuxue ChenSchool of Life Sciences, Shanghai University, 99 Shangda Road, Shanghai China, 200444, P. R. China. chenfuxue@staff.shu.edu.cn.
Shini FengSchool of Life Sciences, Shanghai University, 99 Shangda Road, Shanghai China, 200444, P. R. China. fengshini@shu.edu.cn.

Funding

National Natural Science Foundation of China 52002239Natural Science Foundation of Shanghai 25ZR1402147
6 · The paper itself

Abstract

Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental disorder with limited treatment options, largely due to its complex etiology and the inadequate delivery of therapeutics to the central nervous system. Herein, we report a novel biomimetic nanocomposite, HFn@M/R, designed for the synergistic co-delivery of metformin (Met) and rapamycin (Rapa) to restore neurodevelopmental homeostasis in ASD. Heavy-chain ferritin (HFn) nanocages, produced via an Escherichia coli expression system, were employed as a dual-drug carrier owing to their high drug loading capacity and intrinsic blood-brain barrier permeability via transferrin receptor 1 targeting. Comprehensive physicochemical characterization confirmed structural integrity, optimal drug loading, and redox/pH-responsive release under pathological conditions. In neuronal models, HFn@M/R restored mitochondrial membrane potential, enhanced AMPK-CREB-BDNF signaling, and suppressed mTOR hyperactivation and autophagic blockade. In a valproic acid-induced rat model of ASD, HFn@M/R achieved robust brain accumulation, ameliorated behavioral deficits, and normalized hippocampal electroencephalogram patterns. Transcriptomic analyses further revealed that HFn@M/R modulated key neurodevelopmental, metabolic, and immune pathways, underscoring its capacity to orchestrate a multi-target therapeutic network. Collectively, our findings establish HFn@M/R as a promising precision nanomedicine platform for ASD treatment, with potential applicability to a broad range of neurodevelopmental and neuroinflammatory disorders.

Indexed as

Autism Spectrum DisorderBiomimetic MaterialsFerritinsMetforminSirolimusAnimalsDisease Models, AnimalDrug CarriersDrug Delivery SystemsHomeostasisHumansMaleNanocompositesRatsRats, Sprague-DawleyDrug CarriersFerritinsMetforminSirolimusAMPK/mTOR signaling pathwaysAutism spectrum disorderHeavy-chain ferritin nanocagesMitochondrial dysfunction rescueNeuroinflammation

Identifiers

PMID41083985
PMCPMC12519835

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.