Nanomedicine for Acute Respiratory Distress Syndrome: From Pathophysiological Mechanisms and Disease Heterogeneity to...

Acute respiratory distress syndrome (ARDS) is a life-threatening form of acute respiratory failure characterized by diffuse alveolar injury, severe hypoxemia, and high mortality. Despite advances in supportive care, effective pharmacological interventions remain limited owing to the complex pathophysiology of ARDS, poor pulmonary drug accumulation, systemic adverse effects, and substantial disease heterogeneity. Increasing evidence indicates that distinct clinical and biological subphenotypes of ARDS exhibit differential inflammatory responses, molecular signatures, and therapeutic susceptibilities, underscoring the need for precision medicine approaches. Nanomedicine has emerged as a promising strategy to address these challenges. Through tunable physicochemical properties, surface functionalization, and microenvironment-responsive designs, nanomaterials can enhance drug stability, improve pulmonary targeting, and enable controlled drug release within injured lung tissues. Moreover, nanotherapeutic platforms can exert anti-inflammatory, antioxidant, immunomodulatory, barrier-protective, anticoagulant, and antifibrotic effects through passive and active targeting, biomimetic delivery systems, and stimuli-responsive mechanisms. In this review, we summarize the current understanding of ARDS heterogeneity and its underlying pathophysiological mechanisms, discuss the limitations of existing therapeutic approaches, and comprehensively examine recent advances in nanomaterial-based therapies and targeted drug delivery systems for ARDS. We further highlight key challenges associated with biosafety, large-scale manufacturing, regulatory approval, and clinical translation. Collectively, this review provides a framework for the rational development of precision nanomedicines and outlines future directions for improving therapeutic outcomes in patients with ARDS.