Drug‐Free Biomimetic Oxygen Supply Nanovehicle Promotes Ischemia‐Reperfusion Therapy in Stroke

Author:

He Wenxiu12,Zhang Xiao‐Yong3,Gong Xiang4,Luo Kuankuan1,Mao Xuening5,Lu Enhao1,Chen Yiting1,Wang Rui1,Zhang Zhiwen1,Zhao Jing5,Sha Xianyi1ORCID

Affiliation:

1. Key Laboratory of Smart Drug Delivery (Ministry of Education) Minhang Hospital Institutes of Integrative Medicine Department of Pharmaceutics School of Pharmacy Fudan University Shanghai 201203 China

2. NMPA Key Laboratory for Technology Research and Evaluation of Drug Products Key Laboratory of Chemical Biology (Ministry of Education) School of Pharmaceutical Sciences Cheeloo College of Medicine Shandong University Jinan 250012 China

3. Key Laboratory of Computational Neuroscience and Brain‐Inspired Intelligence (Fudan University) Ministry of Education Shanghai 200433 China

4. State Key Laboratory of Drug Research & Center of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China

5. Department of Neurology Minhang Hospital Fudan University Shanghai 201102 China

Abstract

AbstractRecanalization intervention is the primary recommended therapy for ischemic stroke, but the rapid progression of brain damage results in a very narrow time window for ischemia‐reperfusion therapy, which remains the biggest obstacle for ischemic stroke treatment. Herein, a drug‐free biomimetic nanovehicle capable of improving cerebral ischemic tolerance and thus promoting ischemia‐reperfusion therapy is reported. The nanovehicle comprises an amphiphilic polyfluorocarbon, which delivers oxygen to alleviate the hostile hypoxic environment of ischemic brain, and Pluronic P123, which inhibits matrix metalloproteinase‐9 to protect the blood–brain barrier (BBB). When intravenously injected into ischemic stroke rats with transient middle cerebral artery occlusion, these nanovehicles are able to preferentially access cerebral ischemic lesions in an inflammation‐directed manner, conferring robust ischemic tolerance and reperfusion resistance of brain tissues for ischemia‐reperfusion therapy. Furthermore, it is also demonstrated that the nanovehicle is beneficial for mice with permanent ischemic stroke induced by photothrombosis. This work suggests a promising strategy with hypoxia relief and BBB protection for ischemic stroke therapy.

Publisher

Wiley

Subject

Electrochemistry,Condensed Matter Physics,Biomaterials,Electronic, Optical and Magnetic Materials

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