Anti Irradiation Nanoparticles Shelter Immune Organ from Radio-damage Via Preventing the IKK/IκB/NF-κB Activation

Overview

Journal Mol Cancer

Publisher Biomed Central

Specialties Molecular Biology
Oncology

Date 2024 Oct 18

PMID 39425231

Authors

Shigao Huang

Min Xu

Xiaojun Deng

Qingyue Da

Miaomiao Li

Hao Huang

Lina Zhao

Linlin Jing

Haibo Wang

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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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References

Wang J, Zhu Q, Wang Y, Peng J, Shao L, Li X . Irisin protects against sepsis-associated encephalopathy by suppressing ferroptosis via activation of the Nrf2/GPX4 signal axis. Free Radic Biol Med. 2022; 187:171-184. DOI: 10.1016/j.freeradbiomed.2022.05.023. View

Boraschi D, Italiani P, Weil S, Martin M . The family of the interleukin-1 receptors. Immunol Rev. 2017; 281(1):197-232. DOI: 10.1111/imr.12606. View

Mohammadgholi M, Hosseinimehr S . Crosstalk between Oxidative Stress and Inflammation Induced by Ionizing Radiation in Healthy and Cancerous Cells. Curr Med Chem. 2023; 31(19):2751-2769. DOI: 10.2174/0929867330666230407104208. View

Le Na N, Duc Loc S, Le Minh Tri N, Bich Loan N, Son H, Linh Toan N . Nanomelanin Potentially Protects the Spleen from Radiotherapy-Associated Damage and Enhances Immunoactivity in Tumor-Bearing Mice. Materials (Basel). 2019; 12(10). PMC: 6567087. DOI: 10.3390/ma12101725. View

Pan T, Liu T, Tan S, Wan N, Zhang Y, Li S . Lower Selenoprotein T Expression and Immune Response in the Immune Organs of Broilers with Exudative Diathesis Due to Selenium Deficiency. Biol Trace Elem Res. 2017; 182(2):364-372. DOI: 10.1007/s12011-017-1110-3. View

Lewis S, Williams A, Eisenbarth S . Structure and function of the immune system in the spleen. Sci Immunol. 2019; 4(33). PMC: 6495537. DOI: 10.1126/sciimmunol.aau6085. View

Li W, Wang X, Dong Y, Huo Q, Yue T, Wu X . Nicotinamide riboside intervention alleviates hematopoietic system injury of ionizing radiation-induced premature aging mice. Aging Cell. 2023; 22(11):e13976. PMC: 10652312. DOI: 10.1111/acel.13976. View

Mehdipour A, Yousefi-Ahmadipour A, Kennedy D, Arababadi M . Ionizing radiation and toll like receptors: A systematic review article. Hum Immunol. 2021; 82(6):446-454. DOI: 10.1016/j.humimm.2021.03.008. View

Kohl M, Wiese S, Warscheid B . Cytoscape: software for visualization and analysis of biological networks. Methods Mol Biol. 2010; 696:291-303. DOI: 10.1007/978-1-60761-987-1_18. View

10.

Yan C, Duanmu X, Zeng L, Liu B, Song Z . Mitochondrial DNA: Distribution, Mutations, and Elimination. Cells. 2019; 8(4). PMC: 6523345. DOI: 10.3390/cells8040379. View

11.

Assani G, Segbo J, Yu X, Yessoufou A, Xiong Y, Zhou F . Downregulation of TMPRSS4 Enhances Triple-Negative Breast Cancer Cell Radiosensitivity Through Cell Cycle and Cell Apoptosis Process Impairment. Asian Pac J Cancer Prev. 2019; 20(12):3679-3687. PMC: 7173382. DOI: 10.31557/APJCP.2019.20.12.3679. View

12.

Kobashigawa S, Kashino G, Suzuki K, Yamashita S, Mori H . Ionizing radiation-induced cell death is partly caused by increase of mitochondrial reactive oxygen species in normal human fibroblast cells. Radiat Res. 2015; 183(4):455-64. DOI: 10.1667/RR13772.1. View

13.

Kuo T, Kuo Y, Cho C, Yao C, Lai G, Chuang S . Protective Effect of Extract against Irradiation-Induced Acute Hepatitis. Int J Mol Sci. 2019; 20(4). PMC: 6412687. DOI: 10.3390/ijms20040846. View

14.

Huang S, Xu M, Da Q, Jing L, Wang H . Mitochondria-Targeted Nitronyl Nitroxide Radical Nanoparticles for Protection against Radiation-Induced Damage with Antioxidant Effects. Cancers (Basel). 2024; 16(2). PMC: 10814804. DOI: 10.3390/cancers16020351. View

15.

Yasuda K, Nakanishi K, Tsutsui H . Interleukin-18 in Health and Disease. Int J Mol Sci. 2019; 20(3). PMC: 6387150. DOI: 10.3390/ijms20030649. View

16.

Wilcox C . Effects of tempol and redox-cycling nitroxides in models of oxidative stress. Pharmacol Ther. 2010; 126(2):119-45. PMC: 2854323. DOI: 10.1016/j.pharmthera.2010.01.003. View

17.

Wu Y, Song Y, Wang R, Wang T . Molecular mechanisms of tumor resistance to radiotherapy. Mol Cancer. 2023; 22(1):96. PMC: 10268375. DOI: 10.1186/s12943-023-01801-2. View

18.

Shivappa P, Bernhardt G . Natural Radioprotectors on Current and Future Perspectives: A Mini-Review. J Pharm Bioallied Sci. 2022; 14(2):57-71. PMC: 9416108. DOI: 10.4103/jpbs.jpbs_502_21. View

19.

Kiang J, Zhai M, Liao P, Ho C, Gorbunov N, Elliott T . Thrombopoietin Receptor Agonist Mitigates Hematopoietic Radiation Syndrome and Improves Survival after Whole-Body Ionizing Irradiation Followed by Wound Trauma. Mediators Inflamm. 2017; 2017:7582079. PMC: 5376937. DOI: 10.1155/2017/7582079. View

20.

Conklin K . Chemotherapy-associated oxidative stress: impact on chemotherapeutic effectiveness. Integr Cancer Ther. 2004; 3(4):294-300. DOI: 10.1177/1534735404270335. View