Multifaceted roles of a bioengineered nanoreactor in repressing radiation-induced lung injury.
Biomaterials
; 277: 121103, 2021 10.
Article
in En
| MEDLINE
| ID: mdl-34478930
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pulmonary Fibrosis
/
Radiation Injuries
/
Lung Injury
Limits:
Animals
Language:
En
Journal:
Biomaterials
Year:
2021
Document type:
Article