Nanoscale CaO₂-Loaded Surface-Engineered Iodine-125 Seed with Sustained Self-Oxygenation for Sensitized Tumor...

Iodine-125 (¹²⁵I) brachytherapy (BT) is renowned for its precision and effectiveness in delivering localized radiation doses to solid tumors. However, the therapeutic efficacy of traditional¹²⁵I seed is often limited due to the inherent and acquired radioresistance. Based on the importance of tumor hypoxia in radioresistance, a novel "in situ oxygen-supplement" surface-modified radioactive ¹²⁵I seed (¹²⁵I@TNT-CaO₂) is designed and constructed to overcome hypoxia-induced radioresistance in tumor BT. Titanium dioxide nanotubes (TNTs) are modified on the titanium shell of traditional ¹²⁵I seed and loaded with nanoscale calcium peroxide (CaO₂), further leading to a sustained release of O₂. This in situ oxygen delivery system sensitizes hypoxic tumor regions to ¹²⁵I BT, significantly improving therapeutic efficacy by inducing more ROS generation and DNA damage. Both in vitro and in vivo experiments demonstrate enhanced tumor suppression and apoptosis, with elevated O₂ levels further inhibiting hypoxia-inducible factor 1-alpha (HIF-1α) and its associated signaling pathways. This innovative ¹²⁵I@TNT-CaO₂ seed presents a promising paradigm to enhance the effectiveness of BT by reversing hypoxia-mediated resistance.