Evolution of Nanoparticle Protein Corona across the Blood–Brain Barrier

Engineered
nanoparticles offer the chance to improve drug transport
and delivery through biological barriers, exploiting the possibility
to leave the blood circulation and traverse the endothelial vascular
bed, blood–brain barrier (BBB) included, to reach their target.
It is known that nanoparticles gather molecules on their surface upon
contact with biological fluids, forming the “protein corona”,
which can affect their fate and therapeutic/diagnostic performance,
yet no information on the corona’s evolution across the barrier
has been gathered so far. Using a cellular model of the BBB and gold
nanoparticles, we show that the composition of the corona undergoes
dramatic quantitative and qualitative molecular modifications during
passage from the “blood” to the “brain”
side, while it is stable once beyond the BBB. Thus, we demonstrate
that the nanoparticle corona dynamically and drastically evolves upon
crossing the BBB and that its initial composition is not predictive
of nanoparticle fate and performance once beyond the barrier at the
target organ.