Prior nasal delivery of antagomiR-122 prevents radiation-induced brain injury

• Published in: Molecular therapy Vol. 29; no. 12; pp. 3465 - 3483
• Main Authors: Zhou, Haihong, Sun, Furong, Ou, Mingqian, Zhang, Yu, Lin, Meijun, Song, Liqin, Yu, Yangsheng, Liao, Haojie, Fan, Weihao, Xing, Huaijie, Li, Minhua, Zhao, Kui, Wu, Xiaolian, Sun, Yuanhong, Liang, Chunmei, Cai, Yujie, Cui, Lili
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2021; American Society of Gene & Cell Therapy
• Subjects: Animals; Antagomirs; Brain Injuries; Humans; Mice; microglia; MicroRNAs - genetics; miR-122-5p; nasal delivery; Nasopharyngeal Neoplasms - radiotherapy; Original; Quality of Life; radiation-induced brain injury; radiation-induced brain injury; miR-122-5p; nasal delivery; microglia
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1016/j.ymthe.2021.06.019

Radiation-induced brain injury is a major adverse event in head and neck tumor treatment, influencing the quality of life for the more than 50% of patients who undergo radiation therapy and experience long-term survival. However, no effective treatments are available for these patients, and preventative drugs and effective drug-delivery methods must be developed. Based on our results, miR-122-5p was upregulated in the mouse radiation-induced brain injury (RBI) model and patients with nasopharyngeal carcinoma (NPC) who received radiation therapy. Intranasal administration of a single antagomiR-122-5p dose before irradiation effectively alleviated radiation-induced cognitive impairment, neuronal injury, and neuroinflammation in the mouse RBI model. Results further indicated that miR-122-5p inhibition in microglia reduced the levels of proinflammatory cytokines and enhanced the phagocytic function to protect against radiation-induced neuronal injury in cell models. Further, we profiled transcriptome data and verified that Tensin 1 (TNS1) may be the target of miR-122-5p in RBI. In summary, our results reveal a distinct role for miR-122-5p in regulating neuroinflammation in RBI, indicating that a non-invasive strategy for intranasal miR-122-5p administration may be an attractive therapeutic target in RBI, providing new insights for clinical trials. Further systematic safety assessment, optimization of drug administration, and clarity of mechanism will accelerate the process into clinical practice. [Display omitted] Radiation-induced brain injury is a major adverse event in head and neck tumor treatment, with no effective treatments. Zhou et al. report a non-invasive method to prevent the side effects of radiotherapy by nasal administration targeting miRNA in mouse model, providing a new potential strategy for this kind of clinical treatment.