Impact of therapeutic and environmental nanoparticles on interactions in the local lung environment

This thesis explores airway colonization strategies used by bacteria as a way to improve the design of pulmonary infection therapies. The strategy of most importance here is the targeting of a specific cell receptor known as the platelet activating factor receptor (PAFR). This cell receptor acts as an anchor for certain bacterial pathogens. The use of a biomimetic polymer, poly-2-methacryloyloxyethyl phosphorylcholine (pMPC), was investigated as a coating for nanoparticles to target PAFR and prevent protein fouling. It was first observed using receptor binding models with the program YASARA that pMPC would bind to PAFR slightly better than known PAFR ligands. Further, pMPC with thiol functionality (1.4 kDa) was synthesized through thermally initiated RAFT polymerization and successfully grafted to antimicrobial gold nanoparticles. The subsequent polymer brushes proved effective in decreasing protein adhesion by more than 50%, which could lead to enhanced transport within the lung spaces. The studies conclude with investigation into the role of metal oxide nanoparticles, specifically CuO, in enhancing bacterial infection susceptibility of lung cells. In the immortalized lung epithelial cell line A549, CuO was found to increase adherent bacteria by an order of magnitude at a dose of 0.05 mg/mL. The role of PAFR was confirmed by addition of blocking chemicals to CuO exposed cells challenged with the pneumococci. Overall, these aid our understanding human airway infections and how experimental and modeling studies can aid in the design of synthetic PAFR targeting molecules.