Transport of engineered nanoparticles across human mucus and toxicity to human bronchial epithelial cells in vitro

Increasing demand for nanomaterials creates opportunities for exposure in occupational and non-occupational settings raising concerns about possible health effects. Due to their size, inhaled nanoparticles can deposit in all regions of the human respiratory tract. Unlike the respiratory region, the tracheobronchial airways are protected by mucociliary clearance. Mucus forms a barrier trapping deposited particles limiting interaction with epithelial cells. Although the interaction of mucus with nanoparticles designed for biomedical applications has been recently studies, interactions with nanoparticles in broader commercial use have not been investigated. The purpose of this thesis is to investigate the role of mucus as a barrier to protect the conducting airway epithelium.;We studied a range of nanoparticle types (metal oxides, carbon nanotubes, amorphous silica, and quantum dots), sizes (20-200 nm), shapes (spherical and fibrous), and surface properties (different surface chemistry). A tracking technique was used to directly measure particle movement. In addition, preliminary toxicity assessments were conducted by evaluating cell viability and reactive oxygen production.;Overall we determined that mucus effectively traps nanoparticles. The overwhelming majority of the metal oxide nanoparticles were trapped in mucus. However a small fraction of Zinc Oxide (ZnO) nanoparticles were found to diffuse quickly across mucus layer. Preliminary toxicity assessments indicated that ZnO affects bronchial epithelial cell viability at low doses.;SWCNTs were unable to penetrate mucus and did not affect cell viability. Some amorphous silica (AS) nanoparticles were able to penetrate mucus but the viability of human bronchial epithelial cells was not affected. We also conducted experiments using Quantum dots (QDs) with different surface chemistry. Carboxyl modified QDs were completely trapped in mucus but, polyethylene glycol (PEGylated) coated QDs penetrated human mucus efficiently. Carboxylated QDs had a greater impact on cell viability compared to PEGylated QDs. These experiments suggest that surface chemistry is an important predictor of transport across mucus and toxicity.;My work has shown that mucus is efficient at trapping engineered nanoparticles and that trapping may occur via adhesive interactions between nanoparticle surfaces and mucin fibers. The uptake of nanoparticles and effects on cellular viability could also be affected by nanoparticle surface chemistry.