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作者

Hao Sun, Hui Cai, Chang Xu, Hezheng Zhai, François Lux, Yi Xie, Li Feng, Liqing Du, Yang Liu, Xiaohui Sun, Qin Wang, Huijuan Song, Ningning He, Manman Zhang, Kaihua Ji, Jinhan Wang, Yeqing Gu, Géraldine Leduc, Tristan Doussineau, Yan Wang, Qiang Liu, Olivier Tillement

作者单位

University-CNRS, Lyon University, 69100, Villeurbanne, France. ⁴ Institut Universitaire de France (IUF), 75231, Paris, France. ⁵ Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China. ⁶ Department of Medical Ultrasound, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Abdominal Medical Imaging, Jinan, 250014, China. ⁷ NH TherAguix S.A.S, 29 chemin du Vieux Chêne, 38240, Meylan, France. ⁸ Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300192, China. wangyan@irm-cams.ac.cn. ⁹ Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300192, China. liuqiang@irm-cams.ac.cn. Affiliations ¹ Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300192, China. ² School of Precision Instruments and OPTO-Electronics Engineering, Tianjin University, Tianjin, 300072, China. ³ Institute Light and Mater, UMR5306, Lyo

刊名

Journal of nanobiotechnology

年份

2022

卷号

Vol.20 No.1

页码

449

ISSN

1477-3155

关键词

AGuIX nanoparticles DNA damage repair Ferroptosis Peroxide Radiosensitization.

摘要

In the frame of radiotherapy treatment of cancer, radioresistance remains a major issue that still needs solutions to be overcome. To effectively improve the radiosensitivity of tumors and reduce the damage of radiation to neighboring normal tissues, radiosensitizers have been given increasing attention in recent years. As nanoparticles based on the metal element gadolinium, AGuIX nanoparticles have been shown to increase the radiosensitivity of cancers. Although it is a rare nanomaterial that h...更多

In the frame of radiotherapy treatment of cancer, radioresistance remains a major issue that still needs solutions to be overcome. To effectively improve the radiosensitivity of tumors and reduce the damage of radiation to neighboring normal tissues, radiosensitizers have been given increasing attention in recent years. As nanoparticles based on the metal element gadolinium, AGuIX nanoparticles have been shown to increase the radiosensitivity of cancers. Although it is a rare nanomaterial that has entered preclinical trials, the unclear biological mechanism hinders its further clinical application. In this study, we demonstrated the effectiveness of AGuIX nanoparticles in the radiosensitization of triple-negative breast cancer. We found that AGuIX nanoparticles increased the level of DNA damage by compromising the homologous recombination repair pathway instead of the non-homologous end joining pathway. Moreover, the results showed that AGuIX nanoparticles induced apoptosis, but the degree of apoptosis ability was very low, which cannot fully explain their strong radiosensitizing effect. Ferroptosis, the other mode of cell death, was also discovered to play a significant role in radiation sensitization, and AGuIX nanoparticles may regulate the anti-ferroptosis system by inhibiting the NRF2-GSH-GPX4 signaling pathway.收起

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