Normal tissue and immune organ protection are critical parts of the tumor radiation therapy process. Radiation-induced immune organ damage (RIOD) causes several side reactions by increasing oxidative stress and inflammatory responses, resulting in unsatisfactory curability in tumor radiation therapy. The aim of this study was to develop a novel and efficient anti irradiation nanoparticle and explore its mechanism of protecting splenic tissue from radiation in mice. Nanoparticles of triphenylphosphine cation NIT radicals (NPs-TPP-NIT) were prepared and used to protect the spleens of mice irradiated with X-rays. Splenic tissue histopathology and hematological parameters were investigated to evaluate the protective effect of NPs-TPP-NIT against X-ray radiation. Proteomics was used to identify differentially expressed proteins related to inflammatory factor regulation. In addition, in vitro and in vivo experiments were performed to assess the impact of NPs-TPP-NIT on radiation therapy. NPs-TPP-NIT increased superoxide dismutase, catalase, and glutathione peroxidase activity and decreased malondialdehyde levels and reactive oxygen species generation in the spleens of mice after exposure to 6.0 Gy X-ray radiation. Moreover, NPs-TPP-NIT inhibited cell apoptosis, blocked the activation of cleaved cysteine aspartic acid–specific protease/proteinase, upregulated the expression of Bcl-2, and downregulated that of Bax. We confirmed that NPs-TPP-NIT prevented the IKK/IκB/NF-κB activation induced by ionizing radiation, thereby alleviating radiation-induced splenic inflammatory damage. In addition, when used during radiotherapy for tumors in mice, NPs-TPP-NIT exhibited no significant toxicity and conferred no significant tumor protective effects. NPs-TPP-NIT prevented activation of IKK/IκB/NF-κB signaling, reduced secretion of pro-inflammatory factors, and promoted production of anti-inflammatory factors in the spleen, which exhibited radiation-induced damage repair capability without diminishing the therapeutic effect of radiation therapy. It suggests that NPs-TPP-NIT serve as a potential radioprotective drug to shelter immune organs from radiation-induced damage.

中文翻译：

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抗辐射纳米颗粒通过阻止 IKK/IκB/NF-κB 激活来保护免疫器官免受放射损伤


正常组织和免疫器官保护是肿瘤放射治疗过程的关键部分。辐射诱导的免疫器官损伤 （RIOD） 通过增加氧化应激和炎症反应引起多种副反应，导致肿瘤放射治疗的治愈性不令人满意。本研究的目的是开发一种新型高效的抗辐照纳米颗粒，并探索其保护小鼠脾组织免受辐射的机制。制备了三苯基膦阳离子 NIT 自由基 （NPs-TPP-NIT） 的纳米颗粒，用于保护 X 射线照射小鼠的脾脏。研究脾组织组织病理学和血液学参数，以评价 NPs-TPP-NIT 对 X 射线辐射的保护作用。蛋白质组学用于鉴定与炎症因子调节相关的差异表达蛋白。此外，还进行了体外和体内实验以评估 NPs-TPP-NIT 对放射治疗的影响。NPs-TPP-NIT 在暴露于 6.0 Gy X 射线辐射后增加了小鼠脾脏中的超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶活性，并降低了丙二醛水平和活性氧的产生。此外，NPs-TPP-NIT 抑制细胞凋亡，阻断裂解的半胱氨酸天冬氨酸特异性蛋白酶/蛋白酶的激活，上调 Bcl-2 的表达，下调 Bax 的表达。我们证实 NPs-TPP-NIT 阻止了电离辐射诱导的 IKK/IκB/NF-κB 激活，从而减轻了辐射诱导的脾炎损伤。此外，当在小鼠肿瘤放疗期间使用时，NPs-TPP-NIT 没有表现出显着的毒性，也没有赋予显着的肿瘤保护作用。 NPs-TPP-NIT 阻止 IKK/IκB/NF-κB 信号的激活，减少促炎因子的分泌，促进脾脏中抗炎因子的产生，表现出辐射诱导的损伤修复能力，而不会降低放射治疗的治疗效果。它表明 NPs-TPP-NIT 是一种潜在的放射防护药物，可保护免疫器官免受辐射诱导的损伤。