Screening strategy identified idebenone loaded ROS-responsive nano-polyphenolic vesicle for spinal cord injury therapy

Chenyu Wu; Ximiao Chen; Xiaoying Zhao; Yu Chen; Hao Zhou; Yuxin Deng; Chenchao Li; Yang Huang; Weiyang Gao; Di Zhang; Hongwei Ouyang; Xiaolei Zhang

Materials & Design (Jun 2024)

Screening strategy identified idebenone loaded ROS-responsive nano-polyphenolic vesicle for spinal cord injury therapy

Chenyu Wu,
Ximiao Chen,
Xiaoying Zhao,
Yu Chen,
Hao Zhou,
Yuxin Deng,
Chenchao Li,
Yang Huang,
Weiyang Gao,
Di Zhang,
Hongwei Ouyang,
Xiaolei Zhang

Affiliations

Chenyu Wu: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthopedics, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
Ximiao Chen: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthopedics, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
Xiaoying Zhao: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthopedics, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
Yu Chen: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthopedics, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
Hao Zhou: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthopedics, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
Yuxin Deng: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthopedics, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
Chenchao Li: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthopedics, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
Yang Huang: Department of Orthopaedics, Taizhou Municipal Hospital, Taizhou, Zhejiang Province, China
Weiyang Gao: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthopedics, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Corresponding authors.
Di Zhang: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthopedics, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Corresponding authors.
Hongwei Ouyang: Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Corresponding authors.
Xiaolei Zhang: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthopedics, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Corresponding authors.

Journal volume & issue: Vol. 242
p. 112972

Abstract

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Spinal cord injury (SCI) is a severe central nerve diseases which lacks effective of treatment. Oxidative stress is a major pathological factor for SCI. It may induce mitochondrial damage, which further lead to ferroptosis and apoptosis in neural cells during SCI. Thus, targeting oxidative stress may be the key strategy for SCI treatment. In this study, we carried out screening experiment in the natural product library against oxidative stress in neural cells. It was identified that idebenone (IDE) may potently suppress oxidative stress induced cell death in neural cells. Furthermore, we successfully developed a multifunctional nanovesicles, which we named IDE@PPNs, by encapsulating IDE within proanthocyanidin polyphenol nanovesicles (PPNs). IDE@PPNs exhibited lysosomal escape capability and mitochondrial ROS responsiveness; meanwhile, they may suppress ferroptosis and apoptosis in neural cells. In vivo study demonstrated that IDE@PPNs may promote motor function recovery in rats and suppress ferroptosis and apoptosis in neurons. It may also show high biocompatibility in in vivo study. In summary, we fabricated a novel natural product loaded ROS responsive nanovesicles, IDE@PPNs may have the great potential for SCI therapy.

Published in Materials & Design

ISSN: 0264-1275 (Print); 1873-4197 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials
Website: https://www.journals.elsevier.com/materials-and-design

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