Radioiodine‐Mediated Transition Metal Valence Conversion for Enhanced Chemodynamic Therapy

Abstract Chemodynamic therapy (CDT) presents promise as a cancer treatment method, but its efficacy faces challenges due to the inefficient Fenton catalytic reaction, where the transition metals' conversion from high to low valence states acts as the rate‐limiting step. Here, a strategy employing radioiodine is introduced to facilitate the valence conversion of transition metals for CDT enhancement. Iron‐based metal‐organic framework (MOF) nanoparticles (NPs) are synthesized labeled with radioiodine‐125 (¹²⁵I), referred to as ¹²⁵I‐MIL‐88B(Fe) NPs. These NPs possess a porous structure capable of concentrating and catalyzing H₂O₂ to generate highly toxic hydroxyl radicals (·OH). Furthermore, ¹²⁵I can continuously produce hydrated electrons (e_aq⁻) in aqueous environments, promoting the conversion of Fe³⁺/Fe²⁺ to boost ·OH production. In vitro and in vivo experiments validate the enhanced CDT effect on pancreatic cancer, driven by the reactive oxygen species (ROS)/mitogen‐activated protein kinase (MAPK)/p53 pathway‐mediated cell apoptosis. The radioiodine‐mediated electron‐supplying strategy not only amplifies the effectiveness of CDT but also unlocks new potential applications for radionuclides.