Nanodrug‐Engineered Exosomes Achieve a Jointly Dual‐Pathway Inhibition on Cuproptosis

Abstract Cuproptosis, caused by an intracellular overload of copper (Cu) ions and overexpression of ferredoxin 1 (FDX1), is identified for its regulatory role in the skin wound healing process. This study verifies the presence of cuproptosis in skin wound beds and reactive oxygen species‐induced cel...

Full description

Saved in:
Bibliographic Details
Main Authors: Hanxiao Sun, Yang Zou, Zhengtai Chen, Yan He, Kai Ye, Huan Liu, Lihong Qiu, Yufan Zhang, Yuexue Mai, Xinghong Chen, Zhengwei Mao, Wei Wang, Chenggang Yi
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202413408
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832582777988448256
author Hanxiao Sun
Yang Zou
Zhengtai Chen
Yan He
Kai Ye
Huan Liu
Lihong Qiu
Yufan Zhang
Yuexue Mai
Xinghong Chen
Zhengwei Mao
Wei Wang
Chenggang Yi
author_facet Hanxiao Sun
Yang Zou
Zhengtai Chen
Yan He
Kai Ye
Huan Liu
Lihong Qiu
Yufan Zhang
Yuexue Mai
Xinghong Chen
Zhengwei Mao
Wei Wang
Chenggang Yi
author_sort Hanxiao Sun
collection DOAJ
description Abstract Cuproptosis, caused by an intracellular overload of copper (Cu) ions and overexpression of ferredoxin 1 (FDX1), is identified for its regulatory role in the skin wound healing process. This study verifies the presence of cuproptosis in skin wound beds and reactive oxygen species‐induced cells model. To address the two pathways leading to cell cuproptosis, a nanodrug‐engineered exosomes is proposed. A Cu‐chelator (Clioquinol, CQ) polydopamine (PDA)‐modified stem cell exosome loaded with siRNA‐FDX1, named EXOsiFDX1‐PDA@CQ, is designed to efficiently inhibit the two cuproptosis pathways. The functionalized exosomes are loaded into an injectable hydrogel and applied to treat diabetic wounds in mice and acute skin wounds in pigs. The local and controlled release of EXOsiFDX1‐PDA@CQ ensures the retention of the therapeutic agent at wound beds, effectively promoting wound healing. The strategy of engineered exosomes with functional nanoparticles (NPs) proposed in this study offers an efficient and scalable new approach for regulating cuproptosis.
format Article
id doaj-art-c0e6cc37c1c34fe1a988d7dc75061679
institution Kabale University
issn 2198-3844
language English
publishDate 2025-01-01
publisher Wiley
record_format Article
series Advanced Science
spelling doaj-art-c0e6cc37c1c34fe1a988d7dc750616792025-01-29T09:50:19ZengWileyAdvanced Science2198-38442025-01-01124n/an/a10.1002/advs.202413408Nanodrug‐Engineered Exosomes Achieve a Jointly Dual‐Pathway Inhibition on CuproptosisHanxiao Sun0Yang Zou1Zhengtai Chen2Yan He3Kai Ye4Huan Liu5Lihong Qiu6Yufan Zhang7Yuexue Mai8Xinghong Chen9Zhengwei Mao10Wei Wang11Chenggang Yi12The Second Affiliated Hospital of Zhejiang University College of Medicine Hangzhou 310000 ChinaCollege of Chemical and Biological Engineering Zhejiang University Hangzhou Zhejiang 310027 ChinaThe Second Affiliated Hospital of Zhejiang University College of Medicine Hangzhou 310000 ChinaThe Second Affiliated Hospital of Zhejiang University College of Medicine Hangzhou 310000 ChinaThe Second Affiliated Hospital of Zhejiang University College of Medicine Hangzhou 310000 ChinaThe Second Affiliated Hospital of Zhejiang University College of Medicine Hangzhou 310000 ChinaThe Second Affiliated Hospital of Zhejiang University College of Medicine Hangzhou 310000 ChinaThe Second Affiliated Hospital of Zhejiang University College of Medicine Hangzhou 310000 ChinaThe Second Affiliated Hospital of Zhejiang University College of Medicine Hangzhou 310000 ChinaThe Second Affiliated Hospital of Zhejiang University College of Medicine Hangzhou 310000 ChinaMOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and Engineering Zhejiang University Hangzhou Zhejiang 310027 ChinaThe Second Affiliated Hospital of Zhejiang University College of Medicine Hangzhou 310000 ChinaThe Second Affiliated Hospital of Zhejiang University College of Medicine Hangzhou 310000 ChinaAbstract Cuproptosis, caused by an intracellular overload of copper (Cu) ions and overexpression of ferredoxin 1 (FDX1), is identified for its regulatory role in the skin wound healing process. This study verifies the presence of cuproptosis in skin wound beds and reactive oxygen species‐induced cells model. To address the two pathways leading to cell cuproptosis, a nanodrug‐engineered exosomes is proposed. A Cu‐chelator (Clioquinol, CQ) polydopamine (PDA)‐modified stem cell exosome loaded with siRNA‐FDX1, named EXOsiFDX1‐PDA@CQ, is designed to efficiently inhibit the two cuproptosis pathways. The functionalized exosomes are loaded into an injectable hydrogel and applied to treat diabetic wounds in mice and acute skin wounds in pigs. The local and controlled release of EXOsiFDX1‐PDA@CQ ensures the retention of the therapeutic agent at wound beds, effectively promoting wound healing. The strategy of engineered exosomes with functional nanoparticles (NPs) proposed in this study offers an efficient and scalable new approach for regulating cuproptosis.https://doi.org/10.1002/advs.202413408cuproptosisengineered exosomesFDX1wound healing
spellingShingle Hanxiao Sun
Yang Zou
Zhengtai Chen
Yan He
Kai Ye
Huan Liu
Lihong Qiu
Yufan Zhang
Yuexue Mai
Xinghong Chen
Zhengwei Mao
Wei Wang
Chenggang Yi
Nanodrug‐Engineered Exosomes Achieve a Jointly Dual‐Pathway Inhibition on Cuproptosis
Advanced Science
cuproptosis
engineered exosomes
FDX1
wound healing
title Nanodrug‐Engineered Exosomes Achieve a Jointly Dual‐Pathway Inhibition on Cuproptosis
title_full Nanodrug‐Engineered Exosomes Achieve a Jointly Dual‐Pathway Inhibition on Cuproptosis
title_fullStr Nanodrug‐Engineered Exosomes Achieve a Jointly Dual‐Pathway Inhibition on Cuproptosis
title_full_unstemmed Nanodrug‐Engineered Exosomes Achieve a Jointly Dual‐Pathway Inhibition on Cuproptosis
title_short Nanodrug‐Engineered Exosomes Achieve a Jointly Dual‐Pathway Inhibition on Cuproptosis
title_sort nanodrug engineered exosomes achieve a jointly dual pathway inhibition on cuproptosis
topic cuproptosis
engineered exosomes
FDX1
wound healing
url https://doi.org/10.1002/advs.202413408
work_keys_str_mv AT hanxiaosun nanodrugengineeredexosomesachieveajointlydualpathwayinhibitiononcuproptosis
AT yangzou nanodrugengineeredexosomesachieveajointlydualpathwayinhibitiononcuproptosis
AT zhengtaichen nanodrugengineeredexosomesachieveajointlydualpathwayinhibitiononcuproptosis
AT yanhe nanodrugengineeredexosomesachieveajointlydualpathwayinhibitiononcuproptosis
AT kaiye nanodrugengineeredexosomesachieveajointlydualpathwayinhibitiononcuproptosis
AT huanliu nanodrugengineeredexosomesachieveajointlydualpathwayinhibitiononcuproptosis
AT lihongqiu nanodrugengineeredexosomesachieveajointlydualpathwayinhibitiononcuproptosis
AT yufanzhang nanodrugengineeredexosomesachieveajointlydualpathwayinhibitiononcuproptosis
AT yuexuemai nanodrugengineeredexosomesachieveajointlydualpathwayinhibitiononcuproptosis
AT xinghongchen nanodrugengineeredexosomesachieveajointlydualpathwayinhibitiononcuproptosis
AT zhengweimao nanodrugengineeredexosomesachieveajointlydualpathwayinhibitiononcuproptosis
AT weiwang nanodrugengineeredexosomesachieveajointlydualpathwayinhibitiononcuproptosis
AT chenggangyi nanodrugengineeredexosomesachieveajointlydualpathwayinhibitiononcuproptosis