Coronal ApoE Protein Combines with LRP1 to Inactivate GSK3β That Mitigates Silica Nanoparticle-Induced Brain Lesion

Silica nanoparticles (SiO₂ NPs) are widely used engineered materials that warrant their obvious environmental exposure risk. Our previous study has shown that different routes of SiO₂ NP exposure on the glycogen synthase kinase 3 beta (GSK3β) activity were related to the serum proteins enriched on the surface of SiO₂ NPs, which implied that a particular protein in the serum changed the inherent toxic behavior of SiO₂ NPs and inhibited the activation of GSK3β by SiO₂ NPs. Here, we identified that the SiO₂ NP surface enriched a large amount of apolipoprotein E (ApoE), and the ApoE protein corona bound to the lipoprotein receptor-related protein 1 (LRP1) to inactivate GSK3β, thereby reducing the damage of SiO₂ NPs to the brain. This work presented the first evidence that specific biocorona reduced the toxicity of SiO₂ NPs at the molecular level, which helped to elucidate the role of specific corona components on nanotoxicity.