Silica Nanoparticle Exposure Caused Brain Lesion and Underlying Toxicological Mechanism: Route-Dependent Bio-Corona Formation and GSK3β Phosphorylation Status

When nanoparticles (NPs) enter a physiological environment, they tend to adsorb proteins to form a so-called corona. A comprehensive understanding of the effect of protein corona on NPs' toxicity is required. Our previous study indicated that silica nanoparticles (SiO2 NPs) exposure with different routes resulted in distinct brain damage; however, an exact molecular mechanism of protein corona on the regulation of SiO2 NPs-induced damages needs further investigation. SiO2 NPs exposure via intravenous injection may encounter a protein-rich bio-matrix, which drives the adsorption of serum protein on their surface to form a stable SiO2 NPs@serum complex. On the contrary, SiO2 NPs exposure via intranasal instillation remained their original feature, due to a protein infertile environment of cerebrospinal fluid. Apparently, surface adsorption of proteinaceous substances altered inherent toxic behavior of SiO2 NPs. In addition, glycogen synthase kinase 3 beta (GSK3β) phosphorylate was found at different residues, which play an essential role in orchestrating apoptosis and autophagy threshold. Route-dependent corona formation determined GSK3β phosphorylation status and ultimately the toxic behavior of SiO2 NPs. This work presented the evidence of bio-corona on the regulation of SiO2 NPs-induced toxicity, which can be used to guide risk assessment of environmental NPs.