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 (SiO NPs) exposure with different routes resulted in distinct brain damage; however, an exact molecular mechanism of protein corona on the regulation of SiO NPs-induced damages needs further investigation. SiO NPs exposure intravenous injection may encounter a protein-rich bio-matrix, which drives the adsorption of serum protein on their surface to form a stable SiO NPs@serum complex. On the contrary, SiO NPs exposure 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 SiO 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 SiO NPs. This work presented the evidence of bio-corona on the regulation of SiO NPs-induced toxicity, which can be used to guide risk assessment of environmental NPs.