Paper BI+AS+NS-MoA1
Controlling Bio/Nano Interface Response using Metal Oxide Atomic Layer Deposition: Zinc Oxide ALD Modifies how Human Lung Fibroblasts respond In Vitro to Multiwall Carbon Nanotubes

Monday, November 10, 2014, 2:00 pm, Room 317

Carbon nanotubes have been reported to cause pulmonary fibrosis in mice after inhalation exposure. When inhaled, multiwall carbon nanotubes (MWCNTs) activate macrophage inflammasomes and interleukin (IL)-1β release, key cellular components of the innate immune response. Macrophages are the first line of defense that engulf and remove inhaled MWCNTs from the lungs. Macrophages are also a source of secreted osteopontin (OPN), which promotes tissue matrix remodeling and fibrosis. These responses may be triggered by the unique aspect ratio, aggregation or surface chemistry of MWCNTs. In previous studies, we explored atomic layer deposition (ALD) as a means to modify the surface functionality of MWCNTs and studied how the surface coating affected the toxic response of THP-1 cells, a widely used human monocyte/macrophage cell line, and primary peripheral blood monocytes (PBMCs) obtained from normal human donors. Compared to uncoated MWCNTs, we found that nanotubes with Al₂O₃ nanocoatings showed enhanced IL-1β secretion and decreased OPN production in THP-1 cells and PBMCs, indicating that the coating enhances the innate immune response and decreases pro-fibrotic activity.

In this study we examined the effect of ALD ZnO coatings on the fibrogenic response in human lung fibroblast (HLFs) using mRNA expression and secretion of transforming growth factor (TGF)-b 1 and CXCL10, mediators that promote and deter fibrosis respectively. We find that the ALD ZnO layer thickness can be controlled down to ~5nm, and the thickness scaled directly with the number of ALD cycles, as observed by TEM. Thicker coatings inhibited MWCNT aggregation, and sonication allowed us to induce fiber fragmentation. In this way the ALD coating allowed us to independently adjust surface termination, fiber aggregation, and fiber aspect ratio, providing us a unique tool to examine how each of these factors influences cellular response. Initial results show that the ZnO coating significantly increased TGF-β1 mRNA expression and stimulated a larger pro-fibrogenic response in HLFs compared to uncoated MWCNTs. Control experiments using ZnO nanoparticles also showed potent induction of TGF-β1 mRNA in HLFs. Also, the response tends to correlate with extent of dispersion, and is nearly independent of MWCNT aspect ratio. These experiments show that nanoscale surface functionalization of nanoscale materials may help us gain better understanding of the mechanisms associated with toxicology of nanomaterials, and expand knowledge of biological response at nano/bio interfaces.