Anti irradiation nanoparticles shelter immune organ from radio-damage via preventing the IKK/IκB/NF-κB activation

IF 27.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cancer Pub Date : 2024-10-19 DOI:10.1186/s12943-024-02142-4

Shigao Huang, Min Xu, Xiaojun Deng, Qingyue Da, Miaomiao Li, Hao Huang, Lina Zhao, Linlin Jing, Haibo Wang

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Abstract

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.

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抗辐照纳米粒子通过防止 IKK/IκB/NF-κB 激活来保护免疫器官免受辐射损伤

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率不理想。本研究旨在开发一种新型高效的抗辐照纳米粒子，并探索其保护小鼠脾脏组织免受辐射的机制。制备了三苯基膦阳离子 NIT 自由基纳米粒子（NPs-TPP-NIT），并用于保护接受 X 射线照射的小鼠脾脏。研究了脾组织病理学和血液学参数，以评估 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。经 6.0 Gy X 射线照射后，NPs-TPP-NIT 提高了小鼠脾脏中超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性，降低了丙二醛水平和活性氧的生成。此外，NPs-TPP-NIT 还能抑制细胞凋亡，阻断半胱氨酸天冬氨酸特异性蛋白酶/蛋白酶的活化，上调 Bcl-2 的表达，下调 Bax 的表达。我们证实，NPs-TPP-NIT 能阻止电离辐射诱导的 IKK/IκB/NF-κB 激活，从而减轻辐射诱导的脾脏炎症损伤。此外，在对小鼠进行肿瘤放疗时，NPs-TPP-NIT 没有表现出明显的毒性，也没有显著的肿瘤保护作用。NPs-TPP-NIT 阻止了 IKK/IκB/NF-κB 信号的活化，减少了促炎因子的分泌，促进了脾脏中抗炎因子的产生，显示了放疗引起的损伤修复能力，而不会降低放疗的治疗效果。这表明，NPs-TPP-NIT 可作为一种潜在的辐射防护药物，保护免疫器官免受辐射损伤。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Cancer 医学-生化与分子生物学

CiteScore

54.90

自引率

2.70%

发文量

224

审稿时长

2 months

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