Remodeling the pathological airway: advanced nanotechnology for diagnostics and therapeutics in cystic fibrosis

Cystic fibrosis (CF) constitutes a prototypical lethal genetic disorder characterized by profound pathophysiological barriers that severely compromise both diagnostic performance and targeted therapeutic efficacy. Although the advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulators has revolutionized disease management, the critical clinical imperatives for ultra-sensitive diagnostic modalities and deep pulmonary delivery systems remain largely unmet. This comprehensive review critically evaluates the transformative potential of nanotechnology in remodeling the dual diagnostic and therapeutic landscapes of CF. Initially, we highlight the integration of advanced nanoscale sensors for the real-time and ultra-sensitive profiling of sweat biomarkers, specific genetic mutations, and respiratory metabolites. These innovations fundamentally elevate early diagnostic precision and continuous disease monitoring capabilities. Concurrently, we systematically elucidate how precision-engineered nanocarriers circumvent formidable mucosal and extracellular polymeric substance biofilms. These vehicles facilitate the targeted pulmonary delivery of diverse pharmacological payloads, including CFTR modulators, mucolytics, complex nucleic acid therapeutics and antimicrobial agents. Ultimately, transitioning from engineering conceptualization to clinical application, we dialectically analyze the multifaceted translational hurdles. This review establishes a rigorous roadmap for propelling diagnostic and therapeutic nanomedicine toward clinical accessible realities.