Repurposing clinical iron oxide agents for mild hyperthermia-assisted cancer therapy

作者：Menglei Zha, Jen‐Shyang Ni, Yaxi Li, Feng Chen, Yuling Sheng, Yuying Xu, Qi Liu, Tianyi Kang, Zhipeng Cai, Chong Li, Yang Xu, Decheng Wu, Xingyu Jiang, Changzheng Du, Kai Li · 发表于：Cell Reports Physical Science · 年份：2025 · DOI：10.1016/j.xcrp.2025.102977 · 被引用次数：2 · 研究领域：Nanoparticle-Based Drug Delivery、Ultrasound and Hyperthermia Applications、Cancer Research and Treatments

Cancer remains a global challenge demanding innovative therapeutic strategies, particularly for metastatic cases. While iron oxide nanoparticles have gained clinical approval as iron supplements or imaging contrast agents, their standalone potential for cancer therapy remains largely unexplored. Here, we report that both photo- and ultrasound-induced mild hyperthermia (∼43°C) can enhance iron oxide toxicity through amplified Fenton reactions and sensitize tumor cells to ferroptosis. To enhance translational potential, we refine this platform with a clinically approved iron agent of ferumoxytol and ultrasound, termed ferrultrasonic therapy (FUT). FUT can induce immunogenic cell death across multiple xenograft models and can trigger robust anticancer immune responses. Notably, FUT can significantly prolong the survival time of mice with peritoneal metastasis and achieved a 37.5% complete cure rate by 8 weeks. Overall, our work presents a translatable anticancer strategy validated in patient-derived xenograft humanized mouse models, bridging the gap in repurposing clinically approved iron agents for oncology applications.