Porous Se@SiO 2 Nanoparticles Attenuate Radiation-Induced Cognitive Dysfunction via Modulating Reactive Oxygen Species.

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@SiO 2 nanoparticles (NPs) with antioxidant properties were synthesized. Se@SiO 2 NPs were characterized using X-ray diffraction (XRD) and transmission electron microscopy (TEM). The reactive oxygen species (ROS) scavenging ability of Se@SiO 2 NPs was assessed using a dichloro-dihydro-fluorescein diacetate (DCFH-DA) probe. Apoptosis of HT-22 cells treated with H 2 O 2 and Se@SiO 2 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@SiO 2 NPs were assessed using in vivo imaging system (IVIS). The biosafety and antioxidant effects of Se@SiO 2 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@SiO 2 NPs were successfully synthesized with uniform spherical structures. In vitro, Se@SiO 2 NPs inhibited ROS levels in mouse hippocampal neuronal cell line HT-22 treated with H 2 O 2 . Furthermore, Se@SiO 2 NPs suppressed the apoptotic rate of HT-22 cells by regulating apoptosis-related proteins. Se@SiO 2 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@SiO 2 NPs showed high biocompatibility at a concentration of 1.25 μg/μL. Se@SiO 2 NPs inhibited ROS and promoted neurogenesis in the hippocampus, as well as improved cognitive ability in radiation-induced mice. In conclusion, Se@SiO 2 NPs protected the hippocampus from oxidative stress injury and neuroinflammation. Se@SiO 2 NPs treatment may be a potential therapeutic strategy for radiation-induced cognitive dysfunction.