Warning on the inhalation of silica nanoparticles: Experimental evidence for its easy passage through the air-blood barrier, resulting in systemic distribution and pathological injuries.

As a result of accumulating data, silica nanoparticles (SiNPs) are known to be harmful when inhaled. Nevertheless, the systemic research on its biological processes remains incompletely understood. In our work, we investigated the systemic effects in rats in response to the respiratory exposure of SiNPs, and in-depth clarified the particle distribution in vivo. Moreover, a model of the air-blood barrier was developed to assess the interplay of SiNPs with the epithelium/endothelium interface in vitro. The model was established via a transwell co-culturing of the alveolar epithelium (MLE-12) and the pulmonary microvascular epithelium (MPVECs). Consequently, our data revealed a systemic particle distribution and ensuing multi-tissue pathological injuries in SiNPs-instilled rats, including the heart, spleen, and kidneys. Simultaneously, the translocation of SiNPs passing through the air-blood barrier was verified in vitro. Also, a dose-dependent interruption to the air-blood barrier integrity by SiNPs was noticed in vitro, accompanied by the damage of tight junctions. SiNPs translocation across the air-blood barrier can inevitably facilitate the extra-pulmonary distribution of SiNPs and ensuing systemic effects. Overall, this study provides evidence on the systemic toxicity potential of SiNPs, while highlighting the significance of comprehending SiNPs toxicity and ultimately controlling the health hazards.