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Life sciences · Journal article
Advanced Healthcare Materials · October 9, 2026
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ABSTRACT Chemodynamic therapy (CDT) and brachytherapy face critical challenges, particularly the limited efficiency of Fenton reaction and the insufficient antitumor immunogenicity of brachytherapy. In this study, we employ the metal–organic framework nanocomposite Hf‐TCPP@Fe‐ 99m Tc (where TCPP = tetrakis(4‐carboxyphenyl) porphyrin and 99m Tc = technetium‐99m) for synergistic long‐lasting CDT and immunogenic brachytherapy. Benefiting from the robust interaction between 99m Tc‐emitted γ‐rays and the high‐Z element Hf, the secondary electrons generated during brachytherapy not only damage tumor cells but also establish an electron‐rich microenvironment that drives the continuous reduction of Fe 3+ to Fe 2+, thereby sustaining a highly efficient Fenton reaction. With the generation of hydroxyl radical persisting for over 12 h, this synergistic effect reduced cell viability by an additional 28.6% beyond projections, thereby inducing effective immunogenic cell death, activating a systemic antitumor immune response, and inhibiting both primary and metastatic triple‐negative breast cancer. Through rational design, this work demonstrates that clinically prevalent nontherapeutic γ‐radionuclide can activate long‐lasting CDT and immunogenic brachytherapy to enhance antitumor immunogenicity.