School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 550025, China; Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University (Army Medical University), 400038, Chongqing, China.
Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University (Army Medical University), 400038, Chongqing, China.
Free Radic Biol Med. 2021 Feb 20;164:417-428. doi: 10.1016/j.freeradbiomed.2020.12.435. Epub 2021 Jan 6.
Radiation-induced pulmonary fibrosis (RIPF) is a common complication during thoracic radiotherapy, but there are few effective treatments. Here, we identify IR-780, a mitochondria-targeted near-infrared (NIR) dye, can selectively accumulate in the irradiated lung tissues. Besides, IR-780 significantly alleviates radiation-induced acute lung injury and fibrosis. Furthermore, our results show that IR-780 prevents the differentiation of fibroblasts and the release of pro-fibrotic factors from alveolar macrophages induced by radiation. Besides, IR-780 downregulates the expression of glycolysis-associated genes, and 2-Deoxy-d-glucose (2-DG) also prevents the development of fibrosis in vitro, suggesting radioprotective effects of IR-780 on RIPF might be related to glycolysis regulation. Finally, IR-780 induces tumour cell apoptosis and enhances radiosensitivity in representative H460 and A549 cell lines. These findings indicate that IR-780 is a potential therapeutic small-molecule dye during thoracic radiotherapy.
放射性肺纤维化（RIPF）是胸部放射治疗中的常见并发症，但目前治疗方法有限。本研究发现，一种线粒体靶向近红外（NIR）染料 IR-780 可选择性积聚在受照射的肺组织中。此外，IR-780 可显著减轻放射性急性肺损伤和纤维化。此外，我们的研究结果表明，IR-780 可防止成纤维细胞的分化和肺泡巨噬细胞中促纤维化因子的释放。此外，IR-780 下调糖酵解相关基因的表达，2-脱氧-D-葡萄糖（2-DG）也可防止体外纤维化的发展，提示 IR-780 对 RIPF 的放射防护作用可能与糖酵解调节有关。最后，IR-780 诱导肿瘤细胞凋亡并增强代表性 H460 和 A549 细胞系的放射敏感性。这些发现表明，IR-780 是胸部放射治疗中一种有潜力的治疗性小分子染料。
