Comparison of IgG antibodies and single-domain antibodies (nanobodies and VNARs). (a) Molecular 3D structures of canonical IgG antibody (PDB reference: 1IGT), nanobody (PDB reference: 1I3V), and VNAR (PDB reference: 4HGK). The complementarity determining regions (CDRs), known to be responsible for antigen recognition, are displayed (CDR1, in red; CDR2, in green; CDR3, in blue) [37,38]. (b) Delivery of IgG antibodies and single-domain antibodies (nanobodies and VNARs) at the BBB. The permeability of IgG antibodies is limited due to the presence of Fc receptors (Fcγ receptor, FcγR; neonatal Fc receptor, FcRn). The permeability of single-domain antibodies (nanobodies and VNARs) is facilitated by physiological transcytosis mechanisms. Image created with PyMOL2 and BioRender.com (accessed on 17 June 2021).