Nanomedicine in Lung Transplantation: Emerging Solutions for Clinical Challenges

Lung transplantation (LT) remains the definitive treatment for select patients with end-stage respiratory failure. Despite refinements in donor selection, organ preservation, and perioperative management, LT is still associated with the shortest median survival among all solid organ transplants. Major clinical bottlenecks include airway complications (AC), ischemia-reperfusion injury (IRI), organ rejection and chronic lung allograft dysfunction (CLAD), and suboptimal donor organ quality. Current management is constrained by delayed diagnosis, anatomical delivery barriers, and the off-target toxicities of conventional systemic drug delivery. Nanomedicine, the medical application of nanoscale materials and devices, offers several distinct opportunities in LT: non-invasive detection and imaging of graft injury, protection of unstable cargo, context-specific controlled drug release, and cell-specific targeting. However, clinical translation is still in its early stages, with only liposomal cyclosporine having advanced to phase III clinical trials; most alternative platforms remain preclinical. Here, we categorize the classes of nanomedicines and their specific delivery routes in LT, mapping these technologies onto clinical bottlenecks and critically appraising each platform to frame a path toward clinical translation.