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

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.