Influence of silver doping on pro-inflammatory and pro-fibrogenic effects of nano-titanium dioxide in murine lung

Silver is usually loaded on nano-titanium dioxide (TiO₂ ) through photodeposition method to enhance visible-light catalytic functions for environment purification. However, little is known about how the toxicity changes after silver doping and how the physicochemical properties of loaded components affect nanocomposite toxicity. In this study, Ag-TiO₂ with different sizes and contents of silver particles were obtained by controlling photodeposition time (PDT) and silver addition amount. Pro-inflammatory and pro-fibrogenic responses of these photocatalysts were evaluated in male C57BL/6J murine lung. As a result, silver was well assembled on TiO₂ , promoting visible-light catalytic activity. Notably, the size of silver particles increased with PDT. Meanwhile, toxicity results showed that pure TiO₂ (P25) mainly caused neutrophil infiltration, while 2 wt/wt% silver-loaded TiO₂ recruited more types of inflammatory cells in the lung. Both of them caused the increase of proinflammatory cytokines while decreasing the anti-inflammatory cytokine in bronchoalveolar lavage fluid. However, 2 wt/wt% silver doping also accelerated the lung pro-fibrogenic response of photocatalysts in the subacute phase from evidence of collagen deposition and hydroxyproline concentrations. Mechanistically, the overactivation of TGFBR2 receptors in TGF-β/smads pathways by silver-loaded TiO₂ rather than pure TiO₂ may be the reason why silver-loaded TiO₂ can promote pro-fibrogenic effect response. Intriguingly, the increased toxicity caused by silver doping can be rescued by increasing the size of the loaded silver or decreasing the silver amount. These results may be important for the new understanding of the toxicity of TiO₂ -based photocatalysts.