Uptake, intracellular dissolution, and cytotoxicity of silver nanowires in cell models. (October 2021) - Li, Yiling
Abstract: The uptake, intracellular dissolution, and cytotoxicity of silver nanowires (AgNWs) in two cell models (human keratinocytes - HaCaT cells and murine macrophages) were systemically investigated for the first time. Cellular uptake of AgNWs occurred mainly via pathways of clathrin-dependent endocytosis, caveolae-dependent endocytosis, and phagocytosis. AgNWs could be internalized by two types of cells with numerous lysosomal vesicles detected in close vicinity to AgNWs. Meanwhile, AgNWs exposure caused lysosomal permeabilization and release of cathepsisn B into cytoplasm. Furthermore, for the first time, this study found that AgNWs exposure inhibited the transmembrane ATP binding cassette (ABC) efflux transporter activity, which could make AgNWs as chemosensitizers to increase the toxicity of other xenobiotic pollutants. Toxicity assays evaluating reactive oxygen species production and mitochondrial activity indicated that cytotoxicity differed for different cell types and particles. The intracellular presence of AgNWs with different diameters induced similar toxic events but to different extents. AgNWs were absorbed by macrophages more efficiently than HaCaT cells, while AgNWs exhibited only marginal cytotoxicity towards macrophages compared to HaCaT cells. Using an Ag + fluorescence probe, it was found that a fraction of AgNWs was dissolved inside the lysosomes. A higher amount of released Ag + was detected in HaCaT cells than in macrophages, which might partially contribute to their higher cytotoxicity in HaCaT cells. The toxicity of AgNWs in HaCaT cells and macrophages is due to the high-aspect nature of the nanowires rather than the extracellular release of Ag + . This study may be useful for risk assessments of AgNWs in their practical applications in the biomedical field. Graphical abstract: Image 1 Highlights: Cellular uptake pathways of AgNWs by HaCaT cells and macrophages were investigated. Intracellular dissolved Ag + was visualized by an AIE based luminogen. AgNWs caused lysosomal permeabilization and release of cathepsin B into cytoplasm. AgNWs inhibited ABC efflux transporter activity. Ag + release from AgNWs contributed minor cytotoxicity.