Biomimetic targeted self-adaptive nanodrug for inflammation optimization and AT2 cell modulation in precise ARDS therapy

作者：Cheng Chen, Danfeng He, Xilan Li, Zelin Ou, Hong Wang, Zhinan Shou, Wang Li, Zhengwei Mao, Xiaolan Qi, Jun Deng · 发表于：Science Advances · 年份：2025 · DOI：10.1126/sciadv.adw5133 · 被引用次数：14 · 研究领域：Extracellular vesicles in disease、Nanoplatforms for cancer theranostics、Immune cells in cancer

Acute respiratory distress syndrome (ARDS) is a lethal respiratory condition, while effective pharmacological treatments remain elusive. We identified the decreased mechanical capacity and impaired proliferation of alveolar type 2 (AT2) epithelial cells in the inflammatory environment as the primary contributors to respiratory failure of ARDS. A biomimetic, self-adaptive, 7,8-dihydroxyflavone–loaded hollow mesoporous cerium oxide coated with a platelet membrane (HCeO x -D@PM) was developed for precise ARDS therapy. HCeO x -D@PM comprises a platelet membrane (PM) shell for targeted delivery to injured lungs and an HCeO x core, which enables high drug loading, efficient reactive oxygen species (ROS) scavenging, and penetration of the alveolar-capillary barrier. Initially, HCeO x -D@PM suppresses the inflammation and mitigates the adverse effects of lesions on AT2 cell by scavenging accumulated ROS. It then adaptively releases 7,8-dihydroxyflavone in response to cysteine–aspartic acid protease 3 activation, facilitating AT2 cell proliferation and notably improving survival rates in vivo, offering a promising advancement in the precise treatment of respiratory diseases.