1. Academic Validation
  2. Multifaceted roles of a bioengineered nanoreactor in repressing radiation-induced lung injury

Multifaceted roles of a bioengineered nanoreactor in repressing radiation-induced lung injury

  • Biomaterials. 2021 Oct;277:121103. doi: 10.1016/j.biomaterials.2021.121103.
Tao Liu 1 Qunfang Yang 1 Haiping Zheng 2 Honglin Jia 3 Yufeng He 3 Xuan Zhang 1 Junfeng Zheng 1 Yue Xi 1 Haigang Zhang 1 Renshan Sun 3 Xiaohong Chen 4 Wenjun Shan 5
Affiliations

Affiliations

  • 1 Department of Pharmacology, College of Pharmacy and Laboratory Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, PR China.
  • 2 School of Medicine, Xiamen University, Xiamen, 361102, PR China.
  • 3 Department of Dermatology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, PR China.
  • 4 Department of Pharmacology, College of Pharmacy and Laboratory Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, PR China. Electronic address: pharma821@163.com.
  • 5 Department of Pharmacology, College of Pharmacy and Laboratory Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, PR China. Electronic address: wjshan@tmmu.edu.cn.
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.

Keywords

Alveolar epithelial cell; Cytoprotection; Nanoreactor; Non-erythropoietic EPO derivative; Radiation-induced lung injury.

Figures
Products