Metal-organic framework-based nanoplatforms for acute lung injury: From engineering design to multifunctional therapy

Acute lung injury (ALI) is a critical illness characterized by diffuse alveolar damage, acute inflammatory response, and severe impairment of gas exchange, with high incidence and mortality rates. Currently, no effective targeted therapies are available for ALI. In recent years, metal-organic frameworks (MOFs) have demonstrated unique potential in pulmonary drug delivery owing to their highly tunable structures, exceptionally high specific surface area, and excellent drug-loading and controlled-release capacities. Nevertheless, MOFs still face multiple challenges in pulmonary delivery, including airway barriers, immune clearance, and the inflammatory microenvironment. To address these issues, various engineering strategies have been developed, such as surface modification, biomimetic functionalization, and size and morphology tuning. Furthermore, smart release systems responsive to pH, reactive oxygen species (ROS), and enzymatic activity have been extensively investigated for responsive and controlled delivery drugs in targeting tissues. Notably, the development of MOFs has broadened their therapeutic applications, enabling multifaceted activities such as anti-inflammatory, antioxidant, lung tissue repair, and immunomodulatory effects. In addition, MOFs have shown translational potential in vaccine adjuvant design and aerosol inhalation. This review systematically summarizes the progress of MOFs as pulmonary delivery platforms for ALI treatment, discusses their advantages and limitations, and envisions future advancements through the integration of materials engineering and precision medicine. This work provides a comprehensive perspective on emerging nano-therapeutic strategies for ALI. STATEMENT OF SIGNIFICANCE: This review highlights the emerging role of metal-organic frameworks (MOFs) as multifunctional pulmonary delivery platforms for acute lung injury (ALI). Unlike existing literature that mainly addresses general nanocarriers, we provide a focused and systematic perspective on how MOFs overcome lung-specific barriers, integrate anti-inflammatory and antioxidant functions, and enable precision therapy. By bridging materials engineering with respiratory medicine, this work offers readers novel insights into MOFs' translational potential and their capacity to inspire next-generation nano-therapeutic strategies for ALI.