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However, the extremely hypoxic microenvironment in solid tumors can cause hypoxia\u2010induced radioresistance to <jats:sup>125<\/jats:sup>I brachytherapy, resulting in therapeutic inefficacy. In this study, the aim is to sensitize hypoxic areas in solid tumors using ultrasound\u2010activated oxygen microbubbles for <jats:sup>125<\/jats:sup>I brachytherapy. A modified emulsion freeze\u2010drying method is developed to prepare microbubbles that can be lyophilized for storage and easily reconstituted in situ before administration. The filling gas of the microbubbles is modified by the addition of sulfur hexafluoride to oxygen such that the obtained O<jats:sub>2<\/jats:sub>\/SF<jats:sub>6<\/jats:sub> microbubbles (OS MBs) achieve a much longer half\u2010life (&gt;3\u00d7) than that of oxygen microbubbles. The OS MBs are tested in nasopharyngeal carcinoma (CNE2) tumor\u2010bearing mice and oxygen delivery by the OS MBs induced by ultrasound irradiation relieve hypoxia instantly. The post\u2010treatment results of brachytherapy combined with the ultrasound\u2010triggered OS MBs show a greatly improved therapeutic efficacy compared with brachytherapy\u00a0alone, illustrating ultrasound\u2010mediated oxygen delivery with the developed OS MBs as a promising strategy to improve the therapeutic outcome of <jats:sup>125<\/jats:sup>I brachytherapy in hypoxic tumors.<\/jats:p>","DOI":"10.1002\/advs.202002567","type":"journal-article","created":{"date-parts":[[2021,2,13]],"date-time":"2021-02-13T18:35:18Z","timestamp":1613241318000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["A Robust Oxygen Microbubble Radiosensitizer for Iodine\u2010125 Brachytherapy"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0224-1815","authenticated-orcid":false,"given":"Sheng","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Ultrasound Sun Yat\u2010sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine  Guangzhou 510060 P. 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