Nanoparticle Interactions in Lung Fluid and Lung Mimetic Surfaces – PULMONANO

Objective: This project aims to study the behavior of nanoparticles and formation of nanoparticle corona (NPC) in biomimetic liquid, lung lining fluid (LLF), and on a biomimetic surface, an artificial cilia surface to mimic the ciliated lung epithelium. The interactions of NPs with cells in these environments will be investiated towards nanotoxicology.

Significance: Nanoparticle corona is the dynamical corona of associated biomolecules on a nanoparticle, that determines its biological identity. Current knowledge and efforts on nanoparticle corona studies are limited to use of serum as the biological media, however, lung fluid and lung surfaces should be focused on for understanding how the cell will see the nanoparticle, for the resulting cellular and toxicological response.

Specific Aims: Different sized silica (SiO2) and cerium oxide (CeO2) nanoparticles will be investigated in terms of their aggregation and stability behavior with the formed corona composed of biomolecules that is composed of the real physiological constituents of LLF, in the two different biomimetic millieu: 1) lung fluid as found in the alveolar regions covering the alveolar epithelium, 2) the lung fluid covering the ciliated epithelial tissues of the airway surfaces. The first liquid will be mimicked by proteins and phospholipids purified from porcine lung. The second liquid and the ciliated surface will be mimicked by preparation of magnetically actuatable cilia surface and growing in-situ and ex-situ protein secreting cells on this surface. Nanoparticle corona formations will be studied in both systems, using light scattering, differential sedimentation centrifuge, field flow fractionation, gel electrophoresis to dechiper the corona structure. Also, the behavior of the nanoparticles will be investigated in presence of the artificial cilia beating on the biomimietic cilia surface, in presence of the sol-gel composed of mucus and the periciliary liquid, utilising optical microscopy. Interactions with different types of lung epithelial cells will be investigated towards better characterization of NPC for their toxicological response.

Impact: The project will have a significant impact for both nanotoxicology and nanomedicine, as the fate of the nanoparticles that are deposited in the lungs is strongly dependent on the behavior of NPCs and the interactions in different environments. The project will result in better characterization standards for nanotoxicology studies, as well as aiding in better development of engineered nanoparticles for nanomedicine.