Journal
BIOMATERIALS
Volume 289, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2022.121801
Keywords
Esophageal cancer; 125I brachytherapy; Tumor hypoxia; HIF-1 functional inhibition; Radiosensitizer
Funding
- Jiangsu Province Key Research and Development Plan Program [BE2020785, BE2022855]
- National Natural Science Foundation of China [81971716, 82171922, 82001935]
- ZhiShan Scholar Program of Southeast University [2242022R40069]
- National Key Research and Development Program [2018YFA0704101]
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This study proposes a new strategy to overcome the resistance of esophageal cancer to 125I brachytherapy. By co-encapsulating catalase and a HIF-1 inhibitor into liposomes, researchers were able to generate oxygen and reduce the expression of hypoxia-related proteins, improving the radiosensitivity of brachytherapy and leading to the eradication of esophageal cancer.
Iodine-125 (125I) brachytherapy has become one of the most effective palliative treatment options for advanced esophageal cancer. However, resistance toward 125I brachytherapy caused by pre-existing tumor hypoxia and hypoxia-inducible factor 1 (HIF-1) signaling pathway activation represents a significant limitation in esophageal cancer treatment. To circumvent these problems, herein, we proposed an innovative strategy to alleviate radi-oresistance of brachytherapy by co-encapsulating catalase (CAT) and HIF-1 inhibitor-acriflavine (ACF) into the hydrophilic cavities of liposome, termed as ACF-CAT@Lipo. Under overexpressed H2O2 stimulation in the tumor region, the fabricated ACF-CAT@Lipo can generate an amount of O2 and alleviate tumor hypoxia in vitro and in vivo. Furthermore, cooperating with ACF, the expression of hypoxia-related protein (e.g. HIF-1 alpha, VEGF, MMP-2) are obviously decreased. Importantly, the copious oxygenation and the significant inhibition expression of HIF-1 alpha can further improve the radiosensitivity of 125I brachytherapy and finally realize the eradication of esophageal cancer in vivo. The oxygen enrichment and HIF-1 inhibition function of ACF-CAT@Lipo provides a new strategy to overcome the brachytherapy resistance of esophageal cancer therapy.
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