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However, the therapeutic efficacy of traditional<jats:sup>125<\/jats:sup>I seed\u00a0is\u00a0often limited due to the inherent and acquired radioresistance. Based on the importance of tumor hypoxia in radioresistance, a novel \u201cin situ oxygen\u2010supplement\u201d surface\u2010modified radioactive <jats:sup>125<\/jats:sup>I seed (<jats:sup>125<\/jats:sup>I@TNT\u2010CaO<jats:sub>2<\/jats:sub>) is designed and constructed to overcome hypoxia\u2010induced radioresistance in tumor BT. Titanium dioxide nanotubes (TNTs) are modified on the titanium shell of traditional <jats:sup>125<\/jats:sup>I seed and loaded with nanoscale calcium peroxide (CaO<jats:sub>2<\/jats:sub>), further leading to a sustained release of O<jats:sub>2<\/jats:sub>. This in situ oxygen delivery system sensitizes hypoxic tumor regions to <jats:sup>125<\/jats:sup>I 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 O<jats:sub>2<\/jats:sub> levels further inhibiting hypoxia\u2010inducible factor 1\u2010alpha (HIF\u20101\u03b1) and its associated signaling pathways. This innovative <jats:sup>125<\/jats:sup>I@TNT\u2010CaO<jats:sub>2<\/jats:sub> seed presents a promising paradigm to enhance the effectiveness of BT by reversing hypoxia\u2010mediated resistance.<\/jats:p>","DOI":"10.1002\/smll.202411193","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T20:58:51Z","timestamp":1741726731000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Nanoscale CaO<sub>2<\/sub>\u2010Loaded Surface\u2010Engineered Iodine\u2010125 Seed with Sustained Self\u2010Oxygenation for Sensitized Tumor Brachytherapy"],"prefix":"10.1002","volume":"21","author":[{"given":"Zhongkai","family":"Wang","sequence":"first","affiliation":[{"name":"Center of Interventional Radiology &amp; Vascular Surgery Department of Radiology Zhongda Hospital Medical School Southeast University  Nanjing 210009 P. R. 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