Figure 2.

Blood-brain-barrier (BBB) crossing Nanobodies. (A) The BBB is built by the neurovascular unit consisting of endothelial cells connected via tight junctions, a basal membrane, pericytes and astrocytes foot processes. (B) Various strategies have been applied to shuttle Nbs (VHH) across the BBB: increasing the isoelectric point (pI) to facilitate uptake by endothelial cells (EC); package of Nbs in glutathione coated liposomes and receptor-mediated uptake into EC. Nbs such as the Tmem30a-specific Nb FC5 that target EC membrane receptors can act as Trojan horse to shuttle other Nbs or peptides across the BBB.