Acute lung injury (ALI) is a severe inflammatory lung disease, with high mortality rates. Early intervention by reactive oxygen species (ROS) scavengers could reduce ROS accumulation, break the inflammation expansion chain in alveolar macrophages (AMs), and avoid irreversible damage to alveolar epithelial and endothelial cells. Here, we reported cell-penetrating R9 peptide-modified triangular DNA origami nanostructures (tDONs-R9) as a novel nebulizable drug that could reach the deep alveolar regions and exhibit an enhanced uptake preference of macrophages. tDONs-R9 suppressed the expression of pro-inflammatory cytokines and drove polarization toward the anti-inflammatory M2 phenotype in macrophages. In the LPS-induced ALI mouse model, treatment with nebulized tDONs-R9 alleviated the overwhelming ROS, pro-inflammatory cytokines, and neutrophil infiltration in the lungs. Our study demonstrates that tDONs-R9 has the potential for ALI treatment, and the programmable DNA origami nanostructures provide a new drug delivery platform for pulmonary disease treatment with high delivery efficiency and biosecurity.

中文翻译：

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雾化吸入肽修饰 DNA Origami 可缓解急性肺损伤


急性肺损伤（ALI）是一种严重的炎症性肺部疾病，死亡率很高。活性氧（ROS）清除剂的早期干预可以减少ROS积累，打破肺泡巨噬细胞（AM）中的炎症扩展链，并避免对肺泡上皮和内皮细胞造成不可逆的损伤。在这里，我们报道了细胞穿透性 R9 肽修饰的三角形 DNA 折纸纳米结构 (tDONs-R9) 作为一种新型雾化药物，可以到达深部肺泡区域并表现出增强的巨噬细胞摄取偏好。 tDONs-R9 抑制促炎细胞因子的表达，并推动巨噬细胞中的抗炎 M2 表型极化。在 LPS 诱导的 ALI 小鼠模型中，雾化 tDONs-R9 治疗缓解了肺部大量的 ROS、促炎细胞因子和中性粒细胞浸润。我们的研究表明，tDONs-R9具有治疗ALI的潜力，可编程DNA折纸纳米结构为肺部疾病治疗提供了一种新的药物递送平台，具有高递送效率和生物安全性。