A Novel Self‐Regulated, Non‐Directional Magnetic Thermos‐Brachytherapy 125I Seed Enhances Anticancer Efficacy by Rescuing Immune Escape

This work constructs magnetic nanoparticles (MNPs) and incorporates them with silver rods coated with 125I to form a novel composite seed, which exhibits direction‐independent and self‐regulated heating efficiency, as well as the capacity of preventing MNPs leakage and enabling repeated hyperthermia. Mechanistically, the composite seed‐relied combination therapy enhances anti‐cancer efficacy through rescuing PD‐L1+ neutrophil‐mediated immune escape. Abstract Integrating mild hyperthermia (MH) with 125I brachytherapy holds potential for overcoming treatment resistance and improving anticancer efficacy. Here, magnetic nanoparticles (MNPs) with a suitable Curie temperature are constructed and incorporated with silver rods coated with 125I to form composite seeds. In vitro simulations and in vivo validations demonstrated their effective performance in radiation dose and temperature control. Compared with traditional thermoseeds and previously reported MNPs, this composite seed exhibits direction‐independent and self‐regulated heating efficiency. Additionally, the titanium shell prevented MNPs leakage and enabled its repeated hyperthermia treatment capacity. Subsequently, the enhanced pancancer anticancer efficacy of the composite seed‐relied 125I@MH therapy is confirmed through cellular and animal experiments involving liver cancer and prostate cancer. Further tumor microenvironment investigations based on a subcutaneous liver cancer mouse model identified that 125I therapy recruited Cd274/Pd‐l1+ neutrophils and induced T‐cell exhaustion, leading to immune evasion and brachytherapy resistance. The addition of MH significantly reversed this effect, restoring the function of effector T cells (IFN‐γ+ T cells) and activating T‐cell immunity. In conclusion, this study developed a novel composite seed with superior anticancer efficacy, which holds promising therapeutic potential for the treatment of malignancies, particularly solid tumors, in future clinical practice. This work constructs magnetic nanoparticles (MNPs) and incorporates them with silver rods coated with 125 I to form a novel composite seed, which exhibits direction-independent and self-regulated heating efficiency, as well as the capacity of preventing MNPs leakage and enabling repeated hyperthermia. Mechanistically, the composite seed-relied combination therapy enhances anti-cancer efficacy through rescuing PD-L1 + neutrophil-mediated immune escape. Abstract Integrating mild hyperthermia (MH) with 125 I brachytherapy holds potential for overcoming treatment resistance and improving anticancer efficacy. Here, magnetic nanoparticles (MNPs) with a suitable Curie temperature are constructed and incorporated with silver rods coated with 125 I to form composite seeds. In vitro simulations and in vivo validations demonstrated their effective performance in radiation dose and temperature control. Compared with traditional thermoseeds and previously reported MNPs, this composite seed exhibits direction-independent and self-regulated heating efficiency. Additionally, the titanium shell prevented MNPs leakage and enabled its repeated hyperthermia treatment capacity. Subsequently, the enhanced pancancer anticancer efficacy of the composite seed-relied 125 I@MH therapy is confirmed through cellular and animal experiments involving liver cancer and prostate cancer. Further tumor microenvironment investigations based on a subcutaneous liver cancer mouse model identified that 125 I therapy recruited Cd274/Pd-l1 + neutrophils and induced T-cell exhaustion, leading to immune evasion and brachytherapy resistance. The addition of MH significantly reversed this effect, restoring the function of effector T cells (IFN-γ + T cells) and activating T-cell immunity. In conclusion, this study developed a novel composite seed with superior anticancer efficacy, which holds promising therapeutic potential for the treatment of malignancies, particularly solid tumors, in future clinical practice. Advanced Science, Volume 12, Issue 43, November 20, 2025.