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

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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引用次数: 0

摘要

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。

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

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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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

期刊介绍： Molecular Cancer is a platform that encourages the exchange of ideas and discoveries in the field of cancer research, particularly focusing on the molecular aspects. Our goal is to facilitate discussions and provide insights into various areas of cancer and related biomedical science. We welcome articles from basic, translational, and clinical research that contribute to the advancement of understanding, prevention, diagnosis, and treatment of cancer. The scope of topics covered in Molecular Cancer is diverse and inclusive. These include, but are not limited to, cell and tumor biology, angiogenesis, utilizing animal models, understanding metastasis, exploring cancer antigens and the immune response, investigating cellular signaling and molecular biology, examining epidemiology, genetic and molecular profiling of cancer, identifying molecular targets, studying cancer stem cells, exploring DNA damage and repair mechanisms, analyzing cell cycle regulation, investigating apoptosis, exploring molecular virology, and evaluating vaccine and antibody-based cancer therapies. Molecular Cancer serves as an important platform for sharing exciting discoveries in cancer-related research. It offers an unparalleled opportunity to communicate information to both specialists and the general public. The online presence of Molecular Cancer enables immediate publication of accepted articles and facilitates the presentation of large datasets and supplementary information. This ensures that new research is efficiently and rapidly disseminated to the scientific community.