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 (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.

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“…This is also an important reason we chose AgNPs as carriers to deliver CpG for AS therapy, and the functionalities of such CpG-decorated AgNPs were then examined. To simulate the oxidative stress, the macrophages were stimulated with LPS for activation, and the cytosolic ROS level was assessed using the DCFH-DA probe to produce a green fluorescent signal . Upon LPS stimulation, the cells emitted bright fluorescence, confirming abundant cytosolic ROS generation.…”

“…To simulate the oxidative stress, the macrophages were stimulated with LPS for activation, and the cytosolic ROS level was assessed using the DCFH-DA probe to produce a green fluorescent signal. 38 Upon LPS stimulation, the cells emitted bright fluorescence, confirming abundant cytosolic ROS generation. However, the signal was obviously weakened with both NC-AgNPs and CpG-AgNPs, but the NC DNA and CpG transfected by lipo8000 did not show much change (Figures 4A and S8).…”

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“…However, there are inherent shortcomings of the various imaging modalities, such as FL imaging has inherent penetration depth limitations, PET imaging has low spatial resolution, while PA imaging is difficult to perform whole-body MRI and obtain quantitative images due to its low sensitivity. Multimodality imaging, a combination of imaging modalities, can overcome the limitations of the independent techniques, potentially producing comprehensive anatomical and/or molecular information for improved in vivo imaging. − In the past few years, there has been an explosion of research on the development of multimodal contrast agents . Ye et al developed a glioma-targeting and redox-responsive coassembled nanoparticle (CoNP-RGD1/1) using a coassembly and redox-mediated disassembly strategy.…”

“…168−170 In the past few years, there has been an explosion of research on the development of multimodal contrast agents. 171 Ye et al 172 developed a gliomatargeting and redox-responsive coassembled nanoparticle (CoNP-RGD1/1) using a coassembly and redox-mediated disassembly strategy. Co-NP-RGD 1/1 is able to cross the 10a).…”

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