Figure 5.

Working model of transcytosis-mediated nanoparticle delivery to the brain. Recent study provides evidence that high-affine anti-transferrin receptor IgG conjugated to liposomes mainly undergo transport into the brain at the site of post-capillary venules [14]. This observation counteracts that of unconjugated antibodies that passes the BBB at the site of brain capillaries when designed to be low in affinity or avidity [42]. Targeting the latter antibodies to gold nanoparticles leads to capillary transport in vitro using isolated brain capillaries [58] suggesting that accumulation of targeted nanoparticles in brain parenchyma in vivo may occur via transport across capillaries as well. Studies concerning transport into brain across post-capillary venules using transferrin receptor-targeted low-affine antibodies (lower right) have not been performed but can be stipulated to lead to enhanced transport compared to the use of corresponding antibodies with high affinity. Red bullets: high-affine anti-transferrin receptor IgG conjugated liposomes. Yellow bullets: low-affine or low-avidity anti-transferrin receptor IgG conjugated to liposomes. Drawing created with BioRender, inspired and modified from [14].