Artificial apolipoprotein corona enables nanoparticle brain targeting

Abstract Many potential therapeutic compounds for brain diseases fail to reach their molecular targets due to the impermeability of the blood-brain barrier, limiting their clinical development. Nanotechnology-based approaches might improve compounds pharmacokinetics by enhancing binding to the cerebrovascular endothelium and translocation into the brain. Adsorption of apolipoprotein E4 onto polysorbate 80-stabilized nanoparticles to produce a protein corona allows the specific targeting of cerebrovascular endothelium. This strategy increased nanoparticle translocation into brain parenchyma, and improved brain nanoparticle accumulation 3-fold compared to undecorated particles (119.8 vs 40.5 picomoles). Apolipoprotein decorated nanoparticles have high clinical translational potential and may improve the development of nanotechnology-based medicine for a variety of neurological diseases.