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Porous Se@SiO2 Nanoparticles Attenuate Radiation-Induced Cognitive Dysfunction via Modulating Reactive Oxygen Species

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journal contribution
posted on 2022-03-01, 20:15 authored by Yiwen Zhu, Junjun Zhang, Chunlin Li, Guoying Deng, Junyan Li, Xijian Liu, Bo Wan, Ye Tian
Radiotherapy has been widely used to manage primary and metastatic brain tumors. However, hippocampal damage and subsequent cognitive dysfunction are common complications of whole brain radiation (WBI). In this study, Se@SiO2 nanoparticles (NPs) with antioxidant properties were synthesized. Se@SiO2 NPs were characterized using X-ray diffraction (XRD) and transmission electron microscopy (TEM). The reactive oxygen species (ROS) scavenging ability of Se@SiO2 NPs was assessed using a dichloro-dihydro-fluorescein diacetate (DCFH-DA) probe. Apoptosis of HT-22 cells treated with H2O2 and Se@SiO2 NPs was assessed by annexin V-FITC/PI and JC-1 staining. Western blotting was used to evaluate inflammation-related signaling pathways. In vivo, the distribution and excretion of Se@SiO2 NPs were assessed using in vivo imaging system (IVIS). The biosafety and antioxidant effects of Se@SiO2 NPs were assessed. Neurogenesis in the hippocampus of mice was detected through neuron-specific nuclear protein (NeuN) and 5-bromo-2′-deoxyuridine (BrdU) immunofluorescence staining. The cognitive abilities of mice were also assessed using the Morris water maze test. Results showed that porous Se@SiO2 NPs were successfully synthesized with uniform spherical structures. In vitro, Se@SiO2 NPs inhibited ROS levels in mouse hippocampal neuronal cell line HT-22 treated with H2O2. Furthermore, Se@SiO2 NPs suppressed the apoptotic rate of HT-22 cells by regulating apoptosis-related proteins. Se@SiO2 NPs regulated the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, thereby reducing the expression of inflammatory factors. In vivo, Se@SiO2 NPs showed high biocompatibility at a concentration of 1.25 μg/μL. Se@SiO2 NPs inhibited ROS and promoted neurogenesis in the hippocampus, as well as improved cognitive ability in radiation-induced mice. In conclusion, Se@SiO2 NPs protected the hippocampus from oxidative stress injury and neuroinflammation. Se@SiO2 NPs treatment may be a potential therapeutic strategy for radiation-induced cognitive dysfunction.