The Effect of a Lipid Surface Coating on the Permeation of Upconverting Nanoparticles through a 3D Human Lung Epithelial Model

Preclinical studies of nanoparticles for pulmonary therapeutics are often performed on 2D cell cultures or in vitro models that do not include a mucus barrier. However, the mucus layer lining the lungs is an essential barrier for drugs to permeate in order to exert a therapeutic effect. Herein, the role of surface coating of lanthanide-doped upconverting nanoparticles (UCNPs) and their interaction with the mucus barrier are explored using a patient-derived 3D cell culture model. The upconverted emissions from the UCNPs are used to track them throughout the 3D model and study their localization as a function of administration time and mucus thickness. Positively charged, ligand-free, and negatively charged, supported lipid bilayer-coated UCNPs are evaluated. A substantial difference in the residence time in mucus and mucociliary clearance of each type of UCNP is observed in a realistic and relevant model. As such, these results underscore the need for preclinical investigations in tissue models, especially with respect to the surface properties of the nanoparticles under study. LiYF4:Yb3+,Tm3+ upconverting nanoparticles with and without a supported lipid bilayer coating are evaluated for their ability to penetrate a patient-derived 3D lung epithelium model called MucilAir. Penetration through mucus and cilia-driven mucociliary clearance kinetics indicate a major difference in the fate of the nanoparticles as a function of the different coatings. image

Automated summary

The impact of surface coating on the interaction between lanthanide-doped upconverting nanoparticles (UCNPs) and the mucus barrier is studied using a patient-derived 3D cell culture model. The results demonstrate significant differences in residence time in mucus and mucociliary clearance for UCNPs with different coatings.