Tumor oxygenation nanoliposome synergistic hypoxia-inducible-factor-1 inhibitor enhanced Iodine-125 seed brachytherapy for esophageal cancer

• Published in: Biomaterials 2022-10, Vol.289, p.121801, Article 121801
• Main Authors: Yao, Xijuan, Lu, Shuting, Feng, Cheng, Suo, Ruiyang, Li, Hang, Zhang, Yi, Chen, Qi, Lu, Jian, Wu, Bo, Guo, Jinhe
• Format: Article
• Language: English
• Subjects: 125I brachytherapy; Acriflavine - pharmacology; Brachytherapy; Catalase; Cell Line, Tumor; Esophageal cancer; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - radiotherapy; HIF-1 functional inhibition; Humans; Hydrogen Peroxide; Hypoxia; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Iodine Radioisotopes; Liposomes; Matrix Metalloproteinase 2; Oxygen - metabolism; Radiosensitizer; Tumor hypoxia; Vascular Endothelial Growth Factor A
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2022.121801

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 radioresistance 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-1α, VEGF, MMP-2) are obviously decreased. Importantly, the copious oxygenation and the significant inhibition expression of HIF-1α 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.