journal article·2026-03Open access

Endothelial Cell‐Based Vascular Bandages for Blood–Brain Barrier Repair and Targeted siRNA Delivery

Yaosheng Li, Yunfei Dong, Yaode He, Juanjuan Zheng, Hui Liu, Lu Li, Xiaoxu Hao, Yanli Zhao, Zefeng Yang, Yuankai Sun, Zhiwei Du, Bo Zhao, Weihang Zhou, Honghui Wu, Tianyuan Zhang, Jiahe Wu, Xiangrui Liu, Xianzhen Yin, Zhicai Chen, Rui Xue, Min Lou, Zhen Gu, Xinchi Jiang, Jianqing Gao

Advanced Science· Volume 13· Issue 13

Abstract

ABSTRACT Changes in the blood‐brain barrier (BBB) are key targets for mitigating cerebral ischemia/reperfusion injury. The rapid progression of reperfusion injury necessitates the development of carriers that target and regulate early BBB disruption, while supporting its structure and function during BBB recovery. This study proposes the use of brain microvascular endothelial cell (mECs)‐based vascular bandages carrying siRNAs to simultaneously target, support, and regulate the damaged BBB. Specifically, mECs can target damaged cerebral blood vessels after intravenous injection by interacting with the highly expressed very late antigen ‐ 4 (VLA‐4) in the vessels. Furthermore, by covering the cerebral blood vessels and forming new junction proteins with the vascular endothelium, mECs support the permeability and structural integrity of the vasculature. Additionally, oxygen‐glucose deprivation‐treated mEC culture supernatants (OGD‐SN) can promote connexin 43 (CX43) expression, facilitating the delivery of therapeutic p66 Shc siRNA to the damaged endothelium for BBB regulation. Ultimately, vascular bandage treatment rescued BBB function, alleviated reperfusion injury, and reduced the infarct area. Our study offers a new therapeutic strategy and a novel brain‐targeted delivery platform for treating cerebral ischemia/reperfusion injury.
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Research context

OpenAlex topics: Barrier Structure and Function Studies · RNA Interference and Gene Delivery · Endoplasmic Reticulum Stress and Disease

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

State Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences Zhejiang University Hangzhou Zhejiang P. R. China

Dr. Li Dak Sum & Yip Yio chin Center for Stem Cell and Regenerative Medicine Zhejiang University

Department of Neurology, The Second Affiliated Hospital of Zhejiang University School of Medicine Hangzhou Zhejiang P. R. China

Lingang Laboratory Shanghai P. R. China

Department of Pharmacy, Ningbo Municipal Hospital of Traditional Chinese Medicine (TCM) Affiliated Hospital of Zhejiang Chinese Medical University Ningbo Zhejiang P. R. China

Jinhua Institute of Zhejiang University Jinhua Zhejiang P. R. China

Institute of Innovative Medicine, College of Pharmaceutical Sciences Zhejiang University Hangzhou Zhejiang P. R. China

Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Department of Pharmacy, Affiliated Hangzhou First People's Hospital, School of Medicine Westlake University Hangzhou Zhejiang P. R. China

Innovation Center of Yangtze River Delta Zhejiang University Jiaxing Zhejiang P. R. China

Department of Pharmacy The Second Affiliated Hospital of Zhejiang University School of Medicine Hangzhou Zhejiang P. R. China

Funding

Natural Science Foundation of Zhejiang Province · National Natural Science Foundation of China

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