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已发表论文
功能化自组装 EGCG 纳米颗粒增强 FLASH 放疗的抗肿瘤效应并促进放射免疫治疗
Authors Xu R, Han X, Sun Y, Ma C, Liao S, Yang L, Tang R, Zou Z, Zheng X, Luo H, Gao Y, He X, Li X
Received 30 October 2025
Accepted for publication 22 January 2026
Published 5 February 2026 Volume 2026:21 571116
DOI https://doi.org/10.2147/IJN.S571116
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Yan Shen
Ruiling Xu,1 Xiaowen Han,1 Yunfei Sun,2 Chaofan Ma,2 Shuqing Liao,2 Liu Yang,2 Ruo Tang,2 Zhiyan Zou,1 Xueting Zheng,1 Huiwen Luo,1 Yang Gao,3,4 Xiaozhong He,2 Xiaoan Li1,5
1NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China; 2National Key Laboratory for Shock Wave and Detonation Physics, Institute of Fluid Physics, China Academy of Engineering Physics, Mianyang, Sichuan, 621900, People’s Republic of China; 3Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, Sichuan, 611731, People’s Republic of China; 4Shimmer Center, Tianfu Jiangxi Laboratory, Chengdu, 641419, People’s Republic of China; 5Department of Gastroenterology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China
Correspondence: Xiaozhong He, National Key Laboratory for Shock Wave and Detonation Physics, Institute of Fluid Physics, China Academy of Engineering Physics, Mianyang, Sichuan, 621900, People’s Republic of China, Email hexiaozhong@caep.cn Xiaoan Li, NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China, Email lixiaoan@sc-mch.cn
Background: With the ability to achieve ideal efficacy while significantly reducing radiation damage to normal tissues, ultra-high dose rate radiotherapy (FLASH-RT) is considered one of the most innovative technologies for cancer treatment in the era of precision medicine. However, compared with conventional radiotherapy (CONV-RT), FLASH-RT has not demonstrated superior efficacy in treating tumors.
Methods: We found that the tea polyphenol EGCG could observably promote FLASH-RT X-ray-induced ROS production and DNA damage compared to CONV-RT. A radiosensitizer was further designed by functionalized self-assembled EGCG nanoparticles (named BENPs), aiming to strengthen the anti-tumor effect of FLASH-RT. In vitro experiments such as CCK-8 assay and DNA damage experiment were carried to verify the sensitising effect of BENPs to 4T1 cells. It was further validated in vivo and the molecular mechanism was analyzed using immunofluorescence staining. Biosafety was evaluated by hematoxylin and eosin (H&E) staining and blood routine experiments. Flow cytometry was used to investigate the in vivo immune status of mice triggered by BENPs synergized with FLASH-RT. RNA sequencing assay was employed to estimate the immune response in the spleen of mice.
Results: This combined strategy markedly induced apoptosis and necrosis in tumor cells, which availably inhibited the malignant progression of tumors with good biosafety. More than that, BENPs-assisted FLASH-RT facilitated dendritic cell maturation and increased CD8+ Cytotoxic T cells, B lymphocytes, natural killer and memory T cells differentiation, implying the induction of “positive regulation” of the immune microenvironment, with a better immune prognosis. Meanwhile, the activation of immune regulation was confirmed by effectively upregulation of proinflammatory cytokines in the serum.
Conclusion: Our study suggests that the potential application of BENPs as a sensitizer for FLASH-RT that brings new inspiration for the future clinical application of FLASH-RT therapy.
Keywords: ultra-high dose rate radiotherapy, radiosensitizer, nanoparticles, immune response, tea polyphenol
1NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China; 2National Key Laboratory for Shock Wave and Detonation Physics, Institute of Fluid Physics, China Academy of Engineering Physics, Mianyang, Sichuan, 621900, People’s Republic of China; 3Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, Sichuan, 611731, People’s Republic of China; 4Shimmer Center, Tianfu Jiangxi Laboratory, Chengdu, 641419, People’s Republic of China; 5Department of Gastroenterology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China
Correspondence: Xiaozhong He, National Key Laboratory for Shock Wave and Detonation Physics, Institute of Fluid Physics, China Academy of Engineering Physics, Mianyang, Sichuan, 621900, People’s Republic of China, Email hexiaozhong@caep.cn Xiaoan Li, NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China, Email lixiaoan@sc-mch.cn
Background: With the ability to achieve ideal efficacy while significantly reducing radiation damage to normal tissues, ultra-high dose rate radiotherapy (FLASH-RT) is considered one of the most innovative technologies for cancer treatment in the era of precision medicine. However, compared with conventional radiotherapy (CONV-RT), FLASH-RT has not demonstrated superior efficacy in treating tumors.
Methods: We found that the tea polyphenol EGCG could observably promote FLASH-RT X-ray-induced ROS production and DNA damage compared to CONV-RT. A radiosensitizer was further designed by functionalized self-assembled EGCG nanoparticles (named BENPs), aiming to strengthen the anti-tumor effect of FLASH-RT. In vitro experiments such as CCK-8 assay and DNA damage experiment were carried to verify the sensitising effect of BENPs to 4T1 cells. It was further validated in vivo and the molecular mechanism was analyzed using immunofluorescence staining. Biosafety was evaluated by hematoxylin and eosin (H&E) staining and blood routine experiments. Flow cytometry was used to investigate the in vivo immune status of mice triggered by BENPs synergized with FLASH-RT. RNA sequencing assay was employed to estimate the immune response in the spleen of mice.
Results: This combined strategy markedly induced apoptosis and necrosis in tumor cells, which availably inhibited the malignant progression of tumors with good biosafety. More than that, BENPs-assisted FLASH-RT facilitated dendritic cell maturation and increased CD8+ Cytotoxic T cells, B lymphocytes, natural killer and memory T cells differentiation, implying the induction of “positive regulation” of the immune microenvironment, with a better immune prognosis. Meanwhile, the activation of immune regulation was confirmed by effectively upregulation of proinflammatory cytokines in the serum.
Conclusion: Our study suggests that the potential application of BENPs as a sensitizer for FLASH-RT that brings new inspiration for the future clinical application of FLASH-RT therapy.
Keywords: ultra-high dose rate radiotherapy, radiosensitizer, nanoparticles, immune response, tea polyphenol