Original ArticleThe effects of gold nanoparticles functionalized with ß-amyloid specific peptides on an in vitro model of blood-brain barrier

We studied the effect of gold nanoparticle (AuNP) size, surface charge, concentration and morphology on the integrity of the blood-brain barrier (BBB) in a well-established in vitro model set-up. We focused on the effect of peptide functionalized hollow gold nanospheres and gold nanorods, which selectively bind to amyloidogenic β-amyloid structures. These AuNP conjugates have already been successfully tested as photothermal absorbers for potential application in Alzheimer's disease (AD) therapy in an in vitro set-up, but may exhibit a low passage through the BBB due to their overall negative charge. Our results show that: (i) small (1.4 nm) AuNPs strongly affects the BBB integrity, (ii) negative surface charge impedes BBB passage, and (iii) this charge effect caused by the peptide is compensated by covalent coupling to a polyethylene glycol ligand stabilizing the particles in diluted manner.

Graphical AbstractGold nanoparticles (AuNP) of different size, surface charge, and morphology affect the integrity and thereby the complex electrical impedance of a model blood-brain barrier (BBB) in a different manner. Negative surface charge impedes BBB passage of the particles. This can be compensated by introducing polyethylene glycol ligands, which allows BBB transfer of peptides bound to the AuNP, which selectively can bind to amyloidogenic β-Amyloid structures.47