Hydrogen‐Generating Magnesium Alloy Seed Strand Sensitizes Solid Tumors to Iodine‐125 Brachytherapy

Abstract Radioactive iodine‐125 ( 125 I) seed implantation, a brachytherapy technique, effectively kills tumor cells via X‐rays and gamma rays, serving as an alternative therapeutic option following the failure of frontline treatments for various solid tumors. However, tumor radioresistance limits its efficacy. Hydrogen gas has anticancer properties and can enhance the efficacy of immunotherapy. However, its role in radiotherapy sensitization has rarely been reported. Many current hydrogen delivery methods involve hydrogen‐generating nanomaterials, such as magnesium‐based nanomaterials. This study introduces an AZ31 magnesium alloy 125 I seed strand (termed AMASS) with pH‐dependent slow‐release hydrogen characteristics and excellent mechanical properties. AMASS can be implanted into tumors via minimally invasive surgery, releasing hydrogen around the 125 I seeds. In vitro experiments showed that hydrogen from AMASS degradation significantly inhibited tumor proliferation, increased apoptosis, disrupted redox homeostasis and mitochondrial membrane potential, reduced adenosine triphosphate levels, and induced DNA damage due to 125 I radiation. In mouse xenograft and rabbit liver tumor models, hydrogen from AMASS showed superior therapeutic effects compared with 125 I seeds alone, with no noticeable side effects. In addition, AMASS has a uniform radiation dose distribution and simple implantation. Therefore, hydrogen from AMASS enhanced 125 I seed efficacy, supporting the further promotion and application of 125 I seed implantation in cancer therapy.