Abstract：
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.
摘要：
急性肺损伤(ALI)是一种严重的炎症性肺部疾病,死亡率高。活性氧（ROS）清除剂的早期干预可以减少ROS的积累，打破肺泡巨噬细胞（AMs）的炎症扩展链，并避免对肺泡上皮细胞和内皮细胞的不可逆损伤。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)作为一种新型可雾化药物,可以到达肺泡深部区域,并表现出对巨噬细胞的摄取偏好增强.tDONs-R9抑制促炎细胞因子的表达，并在巨噬细胞中驱动向抗炎M2表型的极化。在LPS诱导的ALI小鼠模型中,雾化TDONS-R9治疗缓解了压倒性的ROS，促炎细胞因子，肺部有嗜中性粒细胞浸润.我们的研究表明，tDONs-R9具有治疗ALI的潜力，可编程的DNA折纸纳米结构为肺部疾病治疗提供了新的药物递送平台，具有高的递送效率和生物安全性。
