Atomic layer deposition coating of carbon nanotubes with zinc oxide causes acute phase immune responses in human monocytes in vitro and in mice after pulmonary exposure

Background: 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. methods: pristine (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. results: ald 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. conclusions: pulmonary 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. © 2016 the author(s).