Gadolinium Oxide Nanoparticles Reinforce the Fractionated Radiotherapy-Induced Immune Response in Tri-Negative Breast Cancer via cGAS-STING Pathway

作者：Boyi Yu, Xuanyi Lu, Xianglong Feng, Ting Zhao, Jiaxin Li, Yudie Lu, Fei Ye, Xiongxiong Liu, Xiaogang Zheng, Zheyu Shen, Xiaodong Jin, Weiqiang Chen, Qiang Li · 发表于：International Journal of Nanomedicine · 年份：2023 · DOI：10.2147/ijn.s428044 · 被引用次数：20 · 研究领域：interferon and immune responses、Nanoplatforms for cancer theranostics、Cancer Research and Treatments

Introduction: 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...