Oxidative stress from reactive oxygen species (ROS) is a reperfusion injury factor that can lead to cell damage and death. Ultrasmall Fe-GA CPNs were synthesized to exert a protective role in ischemic brain neurons via removal of ROS, rescuing of glucose metabolism, and suppressing apoptosis through the upregulation of protein kinase B (Akt), antioxidant nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway.
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.
Author list:
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*
How to cite:
Y. Du, Y. Huo, Q. Yang, Z. Han, L. Hou, B. Cui, K. Fan, Y. Qiu, Z. Chen, W. Huang, J. Lu, L. Cheng, W. Cai, L. Kang, Exploration 2023, 3, 20220041.
https://doi.org/10.1002/EXP.20220041