Background Radiation-induced lung injury (RILI) is a common complication of thoracic radiotherapy and typically progresses from acute radiation pneumonitis to late-stage pulmonary fibrosis. This study investigated whether intranasally delivered Aloe vera -derived nanovesicles (AVNVs) could attenuate early lung injury following high-dose thoracic irradiation. Methods A single-fraction 20 Gy whole-thorax irradiation model was established in C57BL/6 N mice. Mice in the treatment group received intranasal AVNVs at 5 mg kg −1 day −1 for three consecutive days. Histopathological changes were evaluated by H&E staining, and oxidative stress and inflammatory responses were assessed in bronchoalveolar lavage fluid, lung tissue, and serum at an early post-irradiation time point. The uptake of AVNVs by MLE-12 lung epithelial cells and RAW264.7 macrophages was confirmed using flow cytometry and confocal microscopy. In irradiated cells exposed to 8 Gy, γ-H2AX foci were quantified by immunofluorescence, and oxidative stress- and injury-related markers, including SOD, LDH, and GSH, as well as the inflammatory cytokines IL-6 and TNF-α, were measured. Results In vivo, intranasal AVNV administration attenuated early histopathological lung injury, reduced bronchoalveolar lavage fluid protein levels by 42%, and improved oxidative stress- and tissue injury-related indicators, including SOD, GSH, and LDH. AVNVs were efficiently internalized by both MLE-12 cells and RAW264.7 macrophages. In vitro, AVNV pretreatment reduced γ-H2AX expression, alleviated radiation-induced oxidative stress, and decreased IL-6 and TNF-α production. Conclusion Intranasally delivered AVNVs exert early protective effects against radiation-induced lung injury, at least in part by modulating oxidative stress and inflammatory responses. These findings suggest that AVNVs may represent a promising noninvasive candidate for early intervention in RILI. Further studies are warranted to determine whether these early benefits translate into sustained protection against radiation pneumonitis and pulmonary fibrosis.
Zhang et al. (Wed,) studied this question.