Porous Se@SiO₂ 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@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.