Abstract
Exosomes are nanoscale extracellular vesicles secreted by various cell types and have become key mediators of intercellular communication, immune regulation, and tissue regeneration. With advancements in inhalable or nebulized formulations, their potential as therapeutic agents has been significantly enhanced, allowing for targeted delivery to the respiratory system while minimizing systemic side effects. This review provides a comprehensive overview of the fundamental biology, biogenesis, and cargo composition of exosomes, emphasizing their role in intercellular signaling and low immunogenicity. The rationale for local pulmonary delivery is discussed, highlighting advantages such as enhanced bioavailability, reduced systemic exposure, and improved patient compliance. Current preclinical and clinical studies demonstrate the efficacy of inhaled exosomes in treating acute lung injury (ALI), acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), pulmonary fibrosis and lung cancer. Additionally, exosomes exhibit promising immunomodulatory and anti-aging properties, including macrophage polarization, alleviation of cytokine storms, and mitochondrial restoration. Challenges surrounding large-scale production, standardization, and regulatory approval are addressed, while the prospects for engineering exosomes with enhanced payloads and specificity are envisioned. The combination of nanotechnology and biomimetic systems, along with personalized medicine approaches, underscores the transformative potential of inhaled exosomes in respiratory and systemic therapies.