Ultrasmall iron-gallic acid coordination polymer nanodots with antioxidative neuroprotection for PET/MR imaging-guided ischemia stroke therapy.
Yujing DuYan HuoQi YangZhihui HanLinqian HouBixiao CuiKevin FanYongkang QiuZhao ChenWenpeng HuangJie LuLiang ChengWeibo CaiLei KangPublished in: Exploration (Beijing, China) (2023)
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.
Keyphrases
- pet ct
- oxidative stress
- hydrogen peroxide
- reactive oxygen species
- cerebral ischemia
- positron emission tomography
- metal organic framework
- dna damage
- atrial fibrillation
- middle cerebral artery
- cell death
- nuclear factor
- signaling pathway
- visible light
- nitric oxide
- aqueous solution
- cell proliferation
- single cell
- protein kinase
- mesenchymal stem cells
- subarachnoid hemorrhage
- diabetic rats
- cell therapy
- toll like receptor
- heart failure
- inflammatory response
- anti inflammatory
- pi k akt
- computed tomography
- molecular dynamics
- stem cells
- flow cytometry
- acute myocardial infarction
- acute coronary syndrome
- coronary artery disease
- magnetic resonance
- bone marrow
- density functional theory
- iron oxide nanoparticles
- contrast enhanced
- newly diagnosed
- heat stress