International Journal of Nanomedicine (Dec 2023)
Gadolinium Oxide Nanoparticles Reinforce the Fractionated Radiotherapy-Induced Immune Response in Tri-Negative Breast Cancer via cGAS-STING Pathway
Abstract
Boyi Yu,1– 4 Xuanyi Lu,5 Xianglong Feng,1– 4 Ting Zhao,1– 4 Jiaxin Li,1– 4 Yudie Lu,5 Fei Ye,1– 4 Xiongxiong Liu,1– 4 Xiaogang Zheng,1– 4 Zheyu Shen,5 Xiaodong Jin,1– 4 Weiqiang Chen,1– 4 Qiang Li1– 4 1Biomedical Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, People’s Republic of China; 2Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou, People’s Republic of China; 3Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou, Gansu Province, People’s Republic of China; 4College of Life Sciences, University of Chinese Academy of Sciences, Beijing, People’s Republic of China; 5School of Biomedical Engineering, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Xiaodong Jin; Weiqiang Chen, Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Lanzhou, Gansu Province, 730000, People’s Republic of China, Tel +86-931-4969316, Fax +86-931-8272100, Email [email protected]; [email protected]: Radiotherapy is a widely recognized first-line clinical treatment for cancer, but its efficacy may be impeded by the radioresistance of advanced tumors. It is urgent to improve the sensitivity of radioresistant tumors to radiotherapy. In this work, gadolinium oxide nanocrystals (GONs) were utilized as radiosensitizers to enhance the killing effect and reinforce the immune activation of X-ray irradiation on 4T1 breast cancer cells in vitro and in vivo.Methods: 1.0 T small animal MR imaging (MRI) system was employed to trace GONs in vivo, while 225 kVp X-ray irradiation equipment was utilized for investigating the radiosensitization of GONs in 4T1 breast cancer cells in vitro and in vivo. Western blot, quantitative real-time PCR (RT-qPCR), immunohistochemistry, immunofluorescence, clonal survival assay, flow cytometry and reactive oxygen species assay were used to explore the biological mechanism of GON sensitization.Results: GONs exhibited exceptional utility as contrast agents for both in vivo and in vitro MRI imaging. Interestingly, a single dose of 8.0 Gy X-rays together with GONs failed to confer superior therapeutic effects in tumor-bearing mice, while only 3.0 Gy × 3 fractions X-rays combined with GONs exhibited effective tumor growth inhibition. Moreover, fractionated X-ray irradiation with GONs demonstrated a superior capacity to activate the cGAS-STING pathway.Discussion: Fractionated X-ray irradiation in the presence of GONs has demonstrated the most significant activation of the anti-tumor immune response by boosting the cGAS-STING pathway. Keywords: gadolinium oxide nanoparticles, magnetic resonance imaging, radiosensitization, cGAS-STING pathway, 4T1 breast cancer cells
