期刊
ADVANCED SCIENCE
卷 8, 期 7, 页码 -出版社
WILEY
DOI: 10.1002/advs.202002567
关键词
brachytherapy; iodine‐ 125; oxygen microbubbles; tumor hypoxia; ultrasound
资金
- Research Grants Council of Hong Kong under the General Research Fund [16206915]
- Social Development Research Fund from Guangdong Province Science and Technology Bureau [2017B020210004]
- National Natural Science Foundation of China [81871467]
This study aims to sensitize hypoxic areas in solid tumors by utilizing ultrasound-activated oxygen microbubbles for I-125 brachytherapy. The developed O-2/SF6 microbubbles have shown a longer half-life and greatly improved therapeutic efficacy in hypoxic tumors compared to brachytherapy alone in mouse models.
Iodine-125 (I-125) brachytherapy, a promising form of radiotherapy, is increasingly applied in the clinical treatment of a wide range of solid tumors. However, the extremely hypoxic microenvironment in solid tumors can cause hypoxia-induced radioresistance to I-125 brachytherapy, resulting in therapeutic inefficacy. In this study, the aim is to sensitize hypoxic areas in solid tumors using ultrasound-activated oxygen microbubbles for I-125 brachytherapy. A modified emulsion freeze-drying 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-2/SF6 microbubbles (OS MBs) achieve a much longer half-life (>3x) than that of oxygen microbubbles. The OS MBs are tested in nasopharyngeal carcinoma (CNE2) tumor-bearing mice and oxygen delivery by the OS MBs induced by ultrasound irradiation relieve hypoxia instantly. The post-treatment results of brachytherapy combined with the ultrasound-triggered OS MBs show a greatly improved therapeutic efficacy compared with brachytherapy alone, illustrating ultrasound-mediated oxygen delivery with the developed OS MBs as a promising strategy to improve the therapeutic outcome of I-125 brachytherapy in hypoxic tumors.
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