Targeting pulmonary vascular–alveolar coupling in bronchopulmonary dysplasia: Therapeutic mechanisms and translational prospects of extracellular vesicle-based drug delivery

Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in preterm infants, and its primary pathophysiological mechanism consists of an imbalance of the coordinated pulmonary vascular and alveolar development. Extracellular vesicles (EVs), as natural intercellular communication vehicles, demonstrate significant potential in regulating lung development and repair. This review critically synthesizes treatment approaches that target this coupling imbalance in BPD using EV-based drug delivery systems. It focuses on the use of natural EVs, engineered EVs, and drug-loaded EVs in the treatment of BPD, describing how they deliver bioactive molecules, including proteins, lipids, and miRNAs, to regulate endothelial cell function, stimulate angiogenesis, and reduce oxidative stress and inflammation. These actions facilitate repair of the impaired pulmonary vascular network, indirectly promote alveolar development and ultimately restore the alveolar-capillary interface.The therapeutic mechanisms, advantages, drawbacks, present difficulties, and potential optimization paths for these three types of EVs are thoroughly provided in the review. Its purpose is to provide a comprehensive theoretical basis and translational perspective for the development of novel, accurate EV-based BPD therapeutic strategies.