Biomimetic lung-targeted nano drug delivery systems: From chemical biology to respiratory disease therapy.

Respiratory diseases represent a severe global health burden. However, the clinical efficacy of conventional therapeutics is severely limited by complex pulmonary physiological barriers, including mucociliary clearance, alveolar-capillary barrier, and alveolar macrophage phagocytosis. Biomimetic nano drug delivery systems (Nano-DDS) have emerged as a transformative strategy to overcome these obstacles by simulating the structural and functional attributes of biological entities. This review systematically summarizes the design paradigms of lung-targeted Nano-DDS, categorizing them into compositional, morphological, functional, and comprehensive bionics. We critically examine component bionics, utilizing naturally derived viral nanoparticles, cells and extracellular vesicles for their intrinsic biocompatibility. Furthermore, we explore morphological bionics, detailing how mimicking the geometry of pathogens or cells optimizes pulmonary deposition and evades immune surveillance. We then highlight functional bionics, particularly cell membrane camouflage and ligand modification, which disguise synthetic nanoparticles as biological entities to enhance bio-interfacial compatibility and site-specific accumulation. Finally, we discuss the integration of these strategies into comprehensive and intelligent Nano-DDS for precision medicine. By elucidating these bio-inspired mechanisms, this work aims to provide a theoretical framework for overcoming current bottlenecks in pulmonary drug delivery, ultimately facilitating the translation of next-generation therapeutics from bench to bedside.