Multifaceted roles of a bioengineered nanoreactor in repressing radiation-induced lung injury. (October 2021)

• Record Type: Journal Article
• Authors: Liu, Tao; Yang, Qunfang; Zheng, Haiping; Jia, Honglin; He, Yufeng; Zhang, Xuan; Zheng, Junfeng; Xi, Yue; Zhang, Haigang; Sun, Renshan; Chen, Xiaohong; Shan, Wenjun
• Is Part Of: Biomaterials. Volume 277(2021)
• Publication Date: 2021-10
• Subjects: Radiation-induced lung injury -- Nanoreactor -- Cytoprotection -- Non-erythropoietic EPO derivative -- Alveolar epithelial cell; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2021.121103
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: Radiation‐induced lung injury (RILI) is a potentially fatal and dose-limiting complication of thoracic cancer radiotherapy. However, effective therapeutic agents for this condition are limited. Here, we describe a novel strategy to exert additive effects of a non-erythropoietic EPO derivative (ARA290), along with a free radical scavenger, superoxide dismutase (SOD), using a bioengineered nanoreactor (SOD@ARA290-HBc). ARA290-chimeric nanoreactor makes SOD present in a confined reaction space by encapsulation into its interior to heighten stability against denaturing stimuli. In a RILI mouse model, intratracheal administration of SOD@ARA290-HBc was shown to significantly ameliorate acute radiation pneumonitis and pulmonary fibrosis. Our investigations revealed that SOD@ARA290-HBc performs its radioprotective effects by protecting against radiation induced alveolar epithelial cell apoptosis and ferroptosis, suppressing oxidative stress, inhibiting inflammation and by modulating the infiltrated macrophage phenotype, or through a combination of these mechanisms. In conclusion, SOD@ARA29-HBc is a potential therapeutic agent for RILI, and given its multifaceted roles, it may be further developed as a translational nanomedicine for other related disorders.