In vivo biodistribution and synergistic toxicity of silica nanoparticles and cadmium chloride in mice.

Silica nanoparticles (SiNPs) are now in daily use due to their low intrinsic toxicity. Cadmium is a ubiquitous environmental pollutant. In spite of real risk of humans' co-exposure to SiNPs and cadmium, their synergistic toxicity is still unclear. Here, we report the synergistic effects of SiNPs and CdCl₂ on their biodistribution and subacute toxicity in mice. The biodistributions, histopathological changes, serum biochemical parameters and oxidative stress responses were determined after intraperitoneal injection of SiNPs and/or CdCl₂ to mice. SiNPs and CdCl₂ have a positive synergistic toxicity in mice. Although SiNPs were low toxic to mice, co-exposure of SiNPs and CdCl₂ significantly enhanced CdCl₂-induced oxidative damage in the liver as indicated by the severe liver dysfunction and histopathological abnormalities. Co-exposure to SiNPs and CdCl₂ markedly increased the cadmium accumulation in the liver, which induced significant hepatic oxidative stress. In vitro binding assays indicated that serum albumin and Cd(2+) mutually enhanced the binding of each other to SiNPs via the interaction of serum albumin and Cd(2+). The uptake of serum albumin- and Cd(2+)-bound SiNPs by the macrophages significantly increased cadmium accumulation in mice. These results demonstrate that serum albumins play an important role in the positive synergistic toxicity of SiNPs and CdCl₂.