Ultrasmall iron‐gallic acid coordination polymer nanodots with antioxidative neuroprotection for PET/MR imaging‐guided ischemia stroke therapy
Yujing Du,
Yan Huo,
Qi Yang,
Zhihui Han,
Linqian Hou,
Bixiao Cui,
Kevin Fan,
Yongkang Qiu,
Zhao Chen,
Wenpeng Huang,
Jie Lu,
Liang Cheng,
Weibo Cai,
Lei Kang
Affiliations
Yujing Du
Department of Nuclear Medicine Peking University First Hospital Beijing China
Yan Huo
Department of Nuclear Medicine Peking University First Hospital Beijing China
Qi Yang
Department of Nuclear Medicine Peking University First Hospital Beijing China
Zhihui Han
Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology Soochow University Jiangsu China
Linqian Hou
Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology Soochow University Jiangsu China
Bixiao Cui
Department of Radiology and Nuclear Medicine Xuanwu Hospital Capital Medical University Beijing China
Kevin Fan
Departments of Radiology and Medical Physics University of Wisconsin‐Madison Wisconsin USA
Yongkang Qiu
Department of Nuclear Medicine Peking University First Hospital Beijing China
Zhao Chen
Department of Nuclear Medicine Peking University First Hospital Beijing China
Wenpeng Huang
Department of Nuclear Medicine Peking University First Hospital Beijing China
Jie Lu
Department of Radiology and Nuclear Medicine Xuanwu Hospital Capital Medical University Beijing China
Liang Cheng
Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology Soochow University Jiangsu China
Weibo Cai
Departments of Radiology and Medical Physics University of Wisconsin‐Madison Wisconsin USA
Lei Kang
Department of Nuclear Medicine Peking University First Hospital Beijing China
Abstract 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.
