57 Silicon carbide nanowires compromise mucociliary clearance function in human bronchial cells

Abstract Mucociliary clearance in the upper respiratory tract serves as a critical component of the innate immune defence, protecting the lungs from inhaled environmental agents. Disruption of this function increases vulnerability to respiratory infections and chronic diseases. While certain nanomaterials are known to induce pulmonary fibrosis and inflammation, their potential to impair mucociliary function remains insufficiently understood. This study investigated the interactions of silicon- and carbon-based nanomaterials, including silicon carbide nanowires (SiC NWs), silicon dioxide (SiO2), quartz silica DQ12, multiwalled carbon nanotubes (MWCNTs), and graphene nanosheets, with human airway mucus and primary human bronchial epithelial cells. Among the evaluated nanomaterials, only SiC NWs were able to penetrate through the mucus barrier, due to their low silanol group density and hydrophobic surface, which reduced interactions with mucus components. Four consecutive days of repeated exposure of primary human bronchial epithelial cultures to SiC NWs resulted in significant (P < 0.05) impairment of mucociliary clearance, accompanied by abnormal ciliary morphology. Gene expression analysis revealed upregulation of FOXJ1, indicating dysregulated ciliogenesis. Additionally, SiC NWs compromised epithelial barrier integrity and induced pro-inflammatory and pro-fibrotic responses. These findings identify SiC NWs as uniquely capable of penetrating the mucus barrier and disrupting mucociliary clearance function, thereby highlighting a previously underrecognized mechanism of nanomaterial-induced respiratory toxicity. This work underscores the need for careful evaluation of nanomaterial physicochemical properties in relation to airway defence mechanisms.