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. 2021 Jul 31;11(8):1131. doi: 10.3390/biom11081131

Figure 5.

Figure 5

Nanobody BBB permeability due to shuttle-mediated transcytosis. Several molecular entities have been utilized to facilitate the delivery of single-domain antibodies (nanobodies and VNARs) through the BBB into the brain parenchyma. (a) Cell-penetrating peptides (CPPs) carrying nanobodies. The positive charges on their surface mediates their interaction with the cell membrane of the endothelial cells of the BBB. (b) Liposomes and extracellular vesicles carrying nanobodies. The lipophilic nature of these vesicles, in combination with the presence of peptides targeting BBB receptors, allow the brain uptake of nanobodies decorating their inside part or their surface (transferrin receptor-1 (TfR1); lymphocyte function-associated antigen-1 (LFA-1); intercellular adhesion molecule-1 (ICAM-1)). (c) Nanoparticles carrying nanobodies. The multivalent nature of these hybrids allow better BBB penetrance due to an increased binding avidity for targets and blood half-life (magnetic nanoparticles, MNPs; multi-walled carbon nanotubes, MWCNTs). Image created with BioRender.com (accessed on 17 June 2021).