Zhu Yiwen, Zhang Junjun, Li Chunlin, Deng Guoying, Li Junyan, Liu Xijian, Wan Bo, Tian Ye
Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Institute of Radiation Oncology, Soochow University, San Xiang Road No. 1055, Suzhou 215004, Jiangsu, China.
Trauma Center, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201620, China.
ACS Biomater Sci Eng. 2022 Mar 14;8(3):1342-1353. doi: 10.1021/acsbiomaterials.1c01571. Epub 2022 Mar 1.
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 nanoparticles (NPs) with antioxidant properties were synthesized. Se@SiO NPs were characterized using X-ray diffraction (XRD) and transmission electron microscopy (TEM). The reactive oxygen species (ROS) scavenging ability of Se@SiO NPs was assessed using a dichloro-dihydro-fluorescein diacetate (DCFH-DA) probe. Apoptosis of HT-22 cells treated with HO and Se@SiO 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 NPs were assessed using in vivo imaging system (IVIS). The biosafety and antioxidant effects of Se@SiO 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 NPs were successfully synthesized with uniform spherical structures. In vitro, Se@SiO NPs inhibited ROS levels in mouse hippocampal neuronal cell line HT-22 treated with HO. Furthermore, Se@SiO NPs suppressed the apoptotic rate of HT-22 cells by regulating apoptosis-related proteins. Se@SiO 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 NPs showed high biocompatibility at a concentration of 1.25 μg/μL. Se@SiO NPs inhibited ROS and promoted neurogenesis in the hippocampus, as well as improved cognitive ability in radiation-induced mice. In conclusion, Se@SiO NPs protected the hippocampus from oxidative stress injury and neuroinflammation. Se@SiO NPs treatment may be a potential therapeutic strategy for radiation-induced cognitive dysfunction.
放射疗法已被广泛用于治疗原发性和转移性脑肿瘤。然而，海马体损伤及随后的认知功能障碍是全脑放疗（WBI）常见的并发症。在本研究中，合成了具有抗氧化特性的硒@二氧化硅纳米颗粒（NPs）。使用X射线衍射（XRD）和透射电子显微镜（TEM）对硒@二氧化硅纳米颗粒进行表征。使用二氯二氢荧光素二乙酸酯（DCFH-DA）探针评估硒@二氧化硅纳米颗粒的活性氧（ROS）清除能力。通过膜联蛋白V-FITC/PI和JC-1染色评估用HO和硒@二氧化硅纳米颗粒处理的HT-22细胞的凋亡情况。采用蛋白质免疫印迹法评估炎症相关信号通路。在体内，使用体内成像系统（IVIS）评估硒@二氧化硅纳米颗粒的分布和排泄情况。评估了硒@二氧化硅纳米颗粒的生物安全性和抗氧化作用。通过神经元特异性核蛋白（NeuN）和5-溴-2'-脱氧尿苷（BrdU）免疫荧光染色检测小鼠海马体中的神经发生情况。还使用莫里斯水迷宫试验评估小鼠的认知能力。结果表明，成功合成了具有均匀球形结构的多孔硒@二氧化硅纳米颗粒。在体外，硒@二氧化硅纳米颗粒抑制了用HO处理的小鼠海马神经元细胞系HT-22中的ROS水平。此外，硒@二氧化硅纳米颗粒通过调节凋亡相关蛋白抑制了HT-22细胞的凋亡率。硒@二氧化硅纳米颗粒调节核因子κB（NF-κB）和丝裂原活化蛋白激酶（MAPK）信号通路，从而降低炎症因子的表达。在体内，浓度为1.25μg/μL的硒@二氧化硅纳米颗粒表现出高生物相容性。硒@二氧化硅纳米颗粒抑制ROS并促进海马体中的神经发生，以及改善辐射诱导小鼠的认知能力。总之，硒@二氧化硅纳米颗粒保护海马体免受氧化应激损伤和神经炎症。硒@二氧化硅纳米颗粒治疗可能是一种治疗辐射诱导认知功能障碍潜在的治疗策略。
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