Abstract

The lung has been recognized as one of the main target organs for nanoparticles (NPs) exposure. Cellular uptake of nanoparticles into pulmonary components has been routinely evaluated in the conventional monoculture format, which lacks relevant cell to cell communications and interactions that are vital in the physiological environment. A more physiologically relevant co-culture model has thus been developed and described here to study the translocation of NPs across human airway barrier. The model consists of human bronchial epithelial cells (Calu-3), endothelial cells (EA.hy926) and macrophage-like cells (differentiated Thp-1) in a two-chamber system. Silver nanoparticles (AgNPs) coated with tannic acid were used as an example nanoparticle. These AgNPs were applied to the co-culture system where their movement and resultant toxicity were monitored. Cellular uptake and translocation of AgNPs through the modeled barrier were confirmed using analytical methods. Mild cytotoxicity at the given dosage levels was also observed, accompanied by reduced secretion of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α). This human airway model provides researchers with an alternative method for the quantitative evaluation of uptake, translocation and toxicity of aerosol contaminants or nano-sized drug delivery systems in a more relevant in vitro format.

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