Abstract
BackgroundAtomic layer deposition (ALD) is a method for applying conformal nanoscale coatings on three-dimensional structures. We hypothesized that surface functionalization of multi-walled carbon nanotubes (MWCNTs) with polycrystalline ZnO by ALD would alter pro-inflammatory cytokine expression by human monocytes in vitro and modulate the lung and systemic immune response following oropharyngeal aspiration in mice.MethodsPristine (U-MWCNTs) were coated with alternating doses of diethyl zinc and water over increasing ALD cycles (10 to 100 ALD cycles) to yield conformal ZnO-coated MWCNTs (Z-MWCNTs). Human THP-1 monocytic cells were exposed to U-MWCNTs or Z-MWCNTs in vitro and cytokine mRNAs measured by Taqman real-time RT-PCR. Male C57BL6 mice were exposed to U- or Z-MWCNTs by oropharyngeal aspiration (OPA) and lung inflammation evaluated at one day post-exposure by histopathology, cytokine expression and differential counting of cells in bronchoalveolar lavage fluid (BALF) cells. Lung fibrosis was evaluated at 28 days. Cytokine mRNAs (IL-6, IL-1β, CXCL10, TNF-α) in lung, heart, spleen, and liver were quantified at one and 28 days. DNA synthesis in lung tissue was measured by bromodeoxyuridine (BrdU) uptake.ResultsALD resulted in a conformal coating of MWCNTs with ZnO that increased proportionally to the number of coating cycles. Z-MWCNTs released Zn+2 ions in media and increased IL-6, IL-1β, CXCL10, and TNF-α mRNAs in THP-1 cells in vitro. Mice exposed to Z-MWCNTs by OPA had exaggerated lung inflammation and a 3-fold increase in monocytes and neutrophils in BALF compared to U-MWCNTs. Z-MWCNTs, but not U-MWCNTs, induced IL-6 and CXCL10 mRNA and protein in the lungs of mice and increased IL-6 mRNA in heart and liver. U-MWCNTs but not Z-MWCNTs stimulated airway epithelial DNA synthesis in vivo. Lung fibrosis at 28 days was not significantly different between mice treated with U-MWCNT or Z-MWCNT.ConclusionsPulmonary exposure to ZnO-coated MWCNTs produces a systemic acute phase response that involves the release of Zn+2, lung epithelial growth arrest, and increased IL-6. ALD functionalization with ZnO generates MWCNTs that possess increased risk for human exposure.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-016-0141-9) contains supplementary material, which is available to authorized users.
Highlights
Atomic layer deposition (ALD) is a method for applying conformal nanoscale coatings on three-dimensional structures
We previously reported that ALD coating of multi-walled carbon nanotubes (MWCNTs) with aluminum oxide (Al2O3) reduced the ability of MWCNTs to stimulate the production of pro-fibrotic cytokines in cultured human THP-1 monocytic cells in vitro and reduced MWCNTinduced lung fibrosis in mice in vivo [9]
MWCNTs were coated with zinc oxide (ZnO) using ALD in a mesh basket surrounded by polypropylene to yield ZnO-coated MWCNTs (ZMWCNTs)
Summary
Atomic layer deposition (ALD) is a method for applying conformal nanoscale coatings on three-dimensional structures. We hypothesized that surface functionalization of multi-walled carbon nanotubes (MWCNTs) with polycrystalline ZnO by ALD would alter pro-inflammatory cytokine expression by human monocytes in vitro and modulate the lung and systemic immune response following oropharyngeal aspiration in mice. CNTs are used in many different areas including electronics, energy storage, sensors, conductive coatings, capacitors, filtration, and drug delivery [1, 2] Despite these many potential applications, CNTs share geometric similarities with asbestos and there is concern for pulmonary fibrosis, a fatal disease characterized by progressive scar tissue accumulation in the lungs [3]. We sought to examine the effect of ALD coating of MWCNTs with zinc oxide (ZnO) on the inflammatory and fibrogenic response in human monocytic cells in vitro and after delivery to the lungs of C57BL6 mice in vivo by oropharyngeal aspiration (OPA)
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