Nanomedicine-unlocked radiofrequency dynamic therapy dampens incomplete radiofrequency ablation-arised immunosuppression to suppress cancer relapse

Yan Fang; Feixiang Hu; Weiwei Ren; Lihua Xiang; Taixia Wang; Chunyan Zhu; Ruiqing He; Xiulin Dong; Chang Liu; Hong Ding; Kun Zhang

doi:10.1016/j.biomaterials.2025.123087

Nanomedicine-unlocked radiofrequency dynamic therapy dampens incomplete radiofrequency ablation-arised immunosuppression to suppress cancer relapse

Biomaterials. 2025 Jan 2:317:123087. doi: 10.1016/j.biomaterials.2025.123087. Online ahead of print.

Authors

Yan Fang¹, Feixiang Hu², Weiwei Ren³, Lihua Xiang³, Taixia Wang⁴, Chunyan Zhu⁴, Ruiqing He⁵, Xiulin Dong⁴, Chang Liu⁶, Hong Ding⁷, Kun Zhang⁸

Affiliations

¹ Department of Ultrasound, Huashan Hospital, Fudan University, Shanghai, 200040, China. No. 12 Urumqi Middle Road, Shanghai 200040, China; Department of Laboratory Medicine and Department of Ultrasound, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Chengdu, 610072, Sichuan, China.
² Department of Radiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, No. 270 Dong'an Road, Xuhui District, Shanghai, 200032, China.
³ Department of Laboratory Medicine and Department of Ultrasound, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Chengdu, 610072, Sichuan, China; Department of Medical Ultrasound, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, No. 301, Yanchangzhong Road, Shanghai, 200072, China.
⁴ Department of Laboratory Medicine and Department of Ultrasound, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Chengdu, 610072, Sichuan, China.
⁵ Department of Medical Ultrasound, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, No. 301, Yanchangzhong Road, Shanghai, 200072, China.
⁶ Department of Medical Ultrasound, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, No. 301, Yanchangzhong Road, Shanghai, 200072, China. Electronic address: [email protected].
⁷ Department of Ultrasound, Huashan Hospital, Fudan University, Shanghai, 200040, China. No. 12 Urumqi Middle Road, Shanghai 200040, China. Electronic address: [email protected].
⁸ Department of Laboratory Medicine and Department of Ultrasound, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Chengdu, 610072, Sichuan, China. Electronic address: [email protected].

PMID: 39778271
DOI: 10.1016/j.biomaterials.2025.123087

Abstract

Incomplete radiofrequency ablation (iRFA) not only leaves residual tumor, but also render the residual tumor highly self-adaptable and immunosuppressive, consequently expediting residual tumor progression including relapse. To address it, radiofrequency dynamic therapy (RFDT) with identical trigger (namely radiofrequency) has been established and enabled by polyethylene glycol (PEG)-modified Fe-based single atom nanozyme (P@Fe SAZ). P@Fe SAZ can respond to radiofrequency field to produce reactive oxygen species (ROS), attaining the nanomedicine-unlocked low-temperature RFDT. Systematic experiments reveal that ROS further remodels iRFA-potentiated immunosuppressive microenvironment, e.g., expediting tumor-associated macrophages (TAMs) polarization into TAMs-M1, rejecting the intratumoral infiltrations of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). Coincidently, they have been demonstrated to stimulate dendritic cells (DCs) maturation and encourage the proliferations and infiltrations of effector T cells, consequently boosting anti-tumor immune responses and attenuating iRFA-enhanced plasticity, treatment resistance and self-adaptation of residual hepatocellular carcinoma (HCC) after iRFA. Thanks to them, such a nanomedicine-unlocked low-temperature RFDT exerts powerful actions on residual HCC model after iRFA with rapid expansion inhibition, relapse repression, survival prolongation, apoptosis promotion, etc. This low-temperature RFDT opens a window to address the iRFA-enhanced immunosuppression.

Keywords: Fe-based single atom nanozyme; Hepatocellular carcinoma relapse; Immunosuppression; Incomplete radiofrequency ablation; Radiofrequency dynamic therapy.