Advances in Targeted Engineered Nanoparticle-Based Therapeutics for Respiratory Diseases: Current Insights and Future Perspectives

Baiquan Chai,1,* Yuhan Li,2,* Yulong Wang,2,* Danlei Yang,1 Lei Zhang1 1Department of Pulmonary and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2First Clinical College, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei Zhang, Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Tel +86-27-83665522, Email [email protected] Danlei Yang, Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Tel +86-27-83665522, Email [email protected]: Treatments for respiratory diseases, including lung cancer, infectious pulmonary disease, acute respiratory distress syndrome (ARDS) and pulmonary fibrosis remain challenging. Conventional therapy such as inhaled corticosteroids and systemic antibiotics faces limitations of poor bioavailability, nonspecific biodistribution, and inadequate pulmonary barrier penetration, which often lead to suboptimal therapeutic outcomes. Engineered nanoparticles (ENPs) have recently gained significant attention as a potential solution to address these existing challenges. By encapsulating therapeutic agents within lipid-based, polymeric, or inorganic nanostructures, ENPs enable targeted delivery and controlled release, thereby minimizing systemic toxicity and increasing interactions with disease-specific cellular targets. Notably, inhalable ENPs targeting lung cancer cell receptors have demonstrated exceptional ability to penetrate lung barriers, evade clearance, and deliver drugs deep into lung tissue while significantly reducing systemic side effects. Recent advancements in nanotechnology have further broadened their applications in gene therapy, immune modulation and regenerative medicine, such as stem cell-derived extracellular vesicles (EVs) and hydrogel scaffolds for pulmonary tissue repair. This review elucidates therapeutic applications in respiratory diseases, summarizes current advances in formulation design, and discusses translational challenges including nanoparticle heterogeneity, inhalation barriers and gaps in clinical implementation such as reproducibility and scalability, and future directions for clinical translation including reproducibility.Keywords: respiratory diseases, engineered nanoparticles, nanomedicine, drug delivery systems, targeted therapy, regenerative medicine, clinical translation