Optimization of inhalable nanomedicines through the use of multifunctional nanoparticles

Pulmonary administration of nanomedicines, including viral vaccines and treatments for chronic lung diseases, offers a direct, noninvasive route for both systemic delivery and lung-targeted therapy. However, natural lung defense mechanisms often lead to rapid clearance or degradation, limiting clinical translation. This challenge contrasts with the growing burden of lung diseases in aging populations and emerging infectious threats, underscoring the need for optimized pulmonary nanomedicines. We employ bottom-up synthetic protocols to develop multifunctional nanoparticles for imaging, therapy, and the study of nano-biointeractions with the lung environment. Using multiscale models, we study mucus penetration, the composition of the lung surfactant corona, and biodistribution in the lungs. Our findings show how molecular imaging provides insights into lung retention, penetration, and cellular uptake. Moreover, we highlight the use of magnetic separation in studying lung surfactant corona formation. We present multifunctional nanoparticles capable of drug encapsulation and contrast agent labeling, enabling multi-scale characterization of nano-bio interactions. Finally, we show how different surface coatings influence lung retention.