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Ultrasmall iron-gallic acid coordination polymer nanodots with antioxidative neuroprotection for PET/MR imaging-guided ischemia stroke therapy

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机构： [1]Department of Nuclear Medicine Peking University First Hospital Beijing China. [2]Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology Soochow University Jiangsu China. [3]Department of Radiology and Nuclear Medicine Xuanwu Hospital Capital Medical University Beijing China. [4]Departments of Radiology and Medical Physics University of Wisconsin-Madison Wisconsin USA.

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关键词： iron-gallic acid coordination polymer nanodots ischemic/reperfusion injury reactive oxygen species scavenging

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Oxidative stress from reactive oxygen species (ROS) is a reperfusion injury factor that can lead to cell damage and death. Here, ultrasmall iron-gallic acid coordination polymer nanodots (Fe-GA CPNs) were developed as antioxidative neuroprotectors for ischemia stroke therapy guided by PET/MR imaging. As proven by the electron spin resonance spectrum, the ultrasmall Fe-GA CPNs with ultrasmall size, scavenged ROS efficiently. In vitro experiments revealed that Fe-GA CPNs could protect cell viability after being treated with hydrogen peroxide (H2O2) and displayed the effective elimination of ROS by Fe-GA CPNs, which subsequently restores oxidation balance. When analyzing the middle cerebral artery occlusion model, the neurologic damage displayed by PET/MR imaging revealed a distinct recovery after treatment with Fe-GA CPNs, which was proved by 2,3,5-triphenyl tetrazolium chloride staining. Furthermore, immunohistochemistry staining indicated that Fe-GA CPNs inhibited apoptosis through protein kinase B (Akt) restoration, whereas western blot and immunofluorescence indicated the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) pathway following Fe-GA CPNs application. Therefore, Fe-GA CPNs exhibit an impressive antioxidative and neuroprotective role via redox homeostasis recovery by Akt and Nrf2/HO-1 pathway activation, revealing its potential for clinical ischemia stroke treatment.© 2023 The Authors. Exploration published by Henan University and John Wiley & Sons Australia, Ltd.

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第一作者机构： [1]Department of Nuclear Medicine Peking University First Hospital Beijing China.

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通讯机构： [*1]Department of Nuclear Medicine, Peking University First Hospital, No. 8 Xishiku Str., Xicheng Dist., Beijing 100034, China. [*2]600 Highland Avenue, CSC K6/562, Madison, WI 53705-2275, USA [*3]Institute of Functional Nano & Soft Materials (FUNSOM), College of Nano Science & Technology (CNST), Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Jiangsu 215123, China. [*4]Department of Radiology and Nuclear Medicine, Xuanwu Hospital Capital Medical University, Beijing 100053, China.

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Ultrasmall iron-gallic acid coordination polymer nanodots with antioxidative neuroprotection for PET/MR imaging-guided ischemia stroke therapy

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