Integrating magnetic field-initiated thermal-thermodynamic therapy and immune checkpoint blockade to boost antitumor immunotherapy

Cheng Tao; Mei Wen; Pu Qiu; Shining Niu; Xiao Wang; Nuo Yu; Maoquan Li; Zhigang Chen; Long Pan

doi:10.1016/j.jcis.2025.138113

Integrating magnetic field-initiated thermal-thermodynamic therapy and immune checkpoint blockade to boost antitumor immunotherapy

J Colloid Interface Sci. 2025 Jun 6;699(Pt 1):138113. doi: 10.1016/j.jcis.2025.138113. Online ahead of print.

Authors

Cheng Tao¹, Mei Wen², Pu Qiu², Shining Niu², Xiao Wang², Nuo Yu², Maoquan Li³, Zhigang Chen⁴, Long Pan⁵

Affiliations

¹ Department of Interventional and Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; State Key Laboratory of Advanced Fiber Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, China.
² State Key Laboratory of Advanced Fiber Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, China.
³ Department of Interventional and Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
⁴ Department of Interventional and Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; State Key Laboratory of Advanced Fiber Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, China. Electronic address: zgchen@dhu.edu.cn.
⁵ Department of Interventional and Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address: panlong@tongji.edu.cn.

PMID: 40523335
DOI: 10.1016/j.jcis.2025.138113

Abstract

Immune checkpoint blockade (ICB) immunotherapy has transformed cancer treatment by unleashing anti-tumor immune responses. However, its effectiveness in solid tumors is often limited by weak or insufficient immune activation. Herein, an immune-adjuvant strategy has been developed by integrating ICB and alternating magnetic field (AMF) activatable nanoagents to augment antitumor immunotherapy. The AMF-initiated nanoagents are composed of Fe₃O₄ core and mesoporous organosilica shell (MOS) loaded with radical generator 2,2'-azabis(2-imidazoline) dihydrochloride (AIPH), abbreviated as Fe₃O₄@MOS-AIPH. The MOS shell with SSSS- bonds reacts with reductive glutathione (GSH), releasing Fe₃O₄ and AIPH. The Fe₃O₄ can rapidly heat up under AMF irradiation and decompose AIPH into alkyl free radicals, which promotes cell apoptosis via magnetic hyperthermia therapy and thermodynamic therapy (MHT/TDT), thereby effectively inducing immunogenic cell death (ICD) for subsequent dendritic cell maturation. By integrating MHT/TDT and anti-PD-L1 (anti-programmed death-ligand 1 antibody), the antitumor immune response has been greatly enhanced, resulting in the elimination of the primary tumor and effective suppression of distant tumors and lung metastases. The integration of AMF-initiated nanoagents and ICB provides insights into regulating immune cells through multimodal approaches.

Keywords: Immunotherapy; Magnetothermal; Mesoporous organosilica; Tetrasulfide bond; Thermodynamic.