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

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.