Oral Engineered Extracellular Vesicles Based on Ion Exchange Strategy for Multipronged Management of Wilson's Disease Complicated with Reproductive Dysfunction Therapy.

Wang T, Lu W, Cheng Z, Wang L, Jiang Z, Yue Y, Jiang P, Xia Z, He L, Wang F, Wu L, Wang Q, Han H

Advanced science (Weinheim, Baden-Wurttemberg, Germany)17 Jul 2025Cited by 5 (Europe PMC)

PMID40673828PMCIDPMC12520522DOI10.1002/advs.202501689PepBankPUB-40673828

Summary

Wilson's disease (WD), as a typical disease of excessive Cu²⁺ deposition, is characterized by disorders of copper metabolism in the brain and thereby damaging the reproductive system. Conventional interventions using copper chelators can temporarily reduce intracellular copper (in-copper), but continuous re-entry of extracellular copper (ex-copper) into cells results in suboptimal therapy. Effective therapy requires multipronged copper metabolism management. Here, an orally administered, engineered Ganoderma-derived extracellular vesicle (CZGE) is developed for synergistic in/ex-copper regulation. Specifically, CZGE is designed by co-fusing Ganoderma-derived extracellular vesicle (GEVs) and targeted nanomicelles containing zinc-curcumin (Zn-Cur) complex (ZCNs). CZGE, with β-glucan-enriched GEVs and kisspeptin-10-modified ZCNs, can effectively penetrate intestinal and brain barriers after oral administration to target hypothalamic neurons.After internalization, Zn-Cur released from CZGE replaces excess Cu²⁺ to form copper-curcumin (Cu-Cur) and release Zn²⁺ via ion exchange. Cu-Cur reduces in-copper and neuroinflammation via the Nrf2/NLRP3 pathway, while Zn²⁺ inhibits ex-copper influx by activating zinc transporter 1. In WD mice, CZGE alleviates hypothalamic copper deposition, activates ERK1/2 phosphorylation, and repairs reproductive dysfunction by modulating the hypothalamic-pituitary-testicular axis. It first reveals a targeted nanomedicine based on ion exchange that multipronged management in-copper and ex-copper, offering a promising therapeutic strategy for addressing WD with reproductive dysfunction.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone3

In this study, Kisspeptin-10 was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Kisspeptin-10.

01AnimalNot a test of Kisspeptin-10 aloneAnimal study (in vivo)Efficacy outcome
In mice with Wilson's disease, the engineered vesicle CZGE, which carries kisspeptin‑10-modified micelles, alleviated hypothalamic copper deposition.
In plain wordsIn mice with Wilson's disease, a multi-part vesicle product that includes a kisspeptin‑10 label reduced copper build-up in the brain's hypothalamus.
Peptide
Kisspeptin-10
Outcome
DecreaseHypothalamic copper deposition
Study
mousen: not reported in source
Wilson's disease (WD) mice
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
In WD mice, CZGE alleviates hypothalamic copper deposition, activates ERK1/2 phosphorylation, and repairs reproductive dysfunction by modulating the hypothalamic-pituitary-testicular axis.
In this study, Kisspeptin-10 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Kisspeptin-10.
Show in the study text Report a problemFND-4067382801
02AnimalNot a test of Kisspeptin-10 aloneAnimal study (in vivo)Mechanism
In mice with Wilson's disease, the engineered vesicle CZGE, which carries kisspeptin‑10-modified micelles, activated ERK1/2 phosphorylation.
In plain wordsIn mice with Wilson's disease, a multi-part vesicle product that includes a kisspeptin‑10 label switched on a cell-signalling step.
Peptide
Kisspeptin-10
Outcome
IncreaseERK1/2 phosphorylation
Study
mousen: not reported in source
Wilson's disease (WD) mice
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
In WD mice, CZGE alleviates hypothalamic copper deposition, activates ERK1/2 phosphorylation, and repairs reproductive dysfunction by modulating the hypothalamic-pituitary-testicular axis.
In this study, Kisspeptin-10 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Kisspeptin-10.
Show in the study text Report a problemFND-4067382802
03AnimalNot a test of Kisspeptin-10 aloneAnimal study (in vivo)Efficacy outcome
In mice with Wilson's disease, the engineered vesicle CZGE, which carries kisspeptin‑10-modified micelles, repaired reproductive dysfunction by modulating the hypothalamic-pituitary-testicular axis.
In plain wordsIn mice with Wilson's disease, a multi-part vesicle product that includes a kisspeptin‑10 label repaired reproductive problems.
Peptide
Kisspeptin-10
Outcome
DecreaseReproductive dysfunction
Study
mousen: not reported in source
Wilson's disease (WD) mice
Outcome group
Sex hormones and fertility · Reproductive and sexual health
Source sentences
Summary
In WD mice, CZGE alleviates hypothalamic copper deposition, activates ERK1/2 phosphorylation, and repairs reproductive dysfunction by modulating the hypothalamic-pituitary-testicular axis.
In this study, Kisspeptin-10 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Kisspeptin-10.
Show in the study text Report a problemFND-4067382803

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
10 Oct 2026, 09:43 UTC
Study results updated
Version 1
9 Oct 2026, 03:04 UTC
First added · source update from Europe PMC

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