Exosome-camouflaged inhalable (PDSA-HSA) nanocarrier for targeted disulfiram delivery in lung cancer therapy

Lung cancer (LC) remains the principal cause of cancer-related deaths, with current treatment approaches limited by systemic toxicity and drug resistance. In this study, the formation of an inhalable nanocarrier Exo@(PDSA-HSA/DSF), for targeted delivery of disulfiram (DSF) in LC theraphy. The PDSA polymer enables redox-responsive drug release while HSA enhances stability and biocompatibility. Surface modification with tumor-derived exosomes confers biomimetic properties, promoting immune evasion and active targeting of LC cells. Physicochemical analyses confirmed uniform nanosized particles (140-160 nm), with high encapsulation efficiency (82.5 %). The exosome camouflage improved colloidal stability, prolonged drug release, and optimized aerodynamic characteristics favorable for pulmonary delivery. In vitro studies demonstrated enhanced cytotoxicity, elevated ROS production, mitochondrial membrane depolarization, and apoptosis in LC cells, while sparing maintaining normal fibroblasts. The inhalable Exo@(PDSA-HSA/DSF) formulation effectively inhibited tumor growth and prolonged survival in a LC animal model with negligible systemic toxicity. Overall, this exosome-camouflaged PDSA-HSA nanocarriers as an effective platform a promising strategy for targeted inhalation therapy in LC, integrating enhanced drug delivery, tumor efficacy, and excellent biocompatibility.