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

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.