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

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 (H(2)O(2)) 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.