Reduction of Oxidative Stress and Excitotoxicity by Mesenchymal Stem Cell Biomimetic Co‐Delivery System for Cerebral Ischemia‐Reperfusion Injury Treatment

Author:

Zhang Qi1,Li Shengnan1,Chen Hua2,Yin Jiaqing1,Chen Yuqin1,Liu Linfeng1,He Weichong1,Min Zhiyi1,Gong Yue1,Xu Jiangna1,Song Kefan1,Lv Wei3,Xin Hongliang1ORCID

Affiliation:

1. The Affiliated Wuxi People's Hospital of Nanjing Medical University Wuxi People's Hospital Wuxi Medical Center of Nanjing Medical University Pharmacy School of Nanjing Medical University Nanjing 211166 China

2. Department of Neurosurgery The First Affiliated Hospital with Nanjing Medical University Nanjing 210029 China

3. Department of Pharmacy the Affiliated Jiangyin Hospital of Xuzhou Medical University Jiangyin 214400 China

Abstract

AbstractA cerebral ischemia‐reperfusion injury is ensued by an intricate interplay between various pathological processes including excitotoxicity, oxidative stress, inflammation, and apoptosis. For a long time, drug intervention policies targeting a single signaling pathway have failed to achieve the anticipated clinical efficacy in the intricate and dynamic inflammatory environment of the brain. Moreover, inadequate targeted drug delivery remains a significant challenge in cerebral ischemia‐reperfusion injury therapy. In this study, a multifunctional nanoplatform (designated as PB‐006@MSC) is developed using ZL006‐loaded Prussian blue nanoparticles (PBNPs) camouflaged by a mesenchymal stem cell (MSC) membrane (MSCm). ZL006 is a neuroprotectant. It can be loaded efficiently into the free radical scavenger PBNP through mesoporous adsorption. This can simultaneously modulate multiple targets and pathways. MSCm biomimetics can reduce the nanoparticle immunogenicity, efficiently enhance their homing capability to the cerebral ischemic penumbra, and realize active‐targeting therapy for ischemic stroke. In animal experiments, PB‐006@MSC integrated reactive oxygen species (ROS) scavenging and neuroprotection. Thereby, it selectively targeted the cerebral ischemic penumbra (about fourfold higher accumulation at 24 h than in the non‐targeted group), demonstrated a remarkable therapeutic efficacy in reducing the volume of cerebral infarction (from 37.1% to 2.3%), protected the neurogenic functions, and ameliorated the mortality.

Funder

National Natural Science Foundation of China

Publisher

Wiley

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