Intranasal administration of Aloe-derived nanovesicles attenuates early radiation-induced lung injury

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.

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.

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.

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.