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

Abstract

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 <i>via</i> 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 <i>via</i> 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.