Figure 1. Model of receptor-mediated transcytosis of transferrin-containing nanoparticles. Transferrin and its receptor are one of the ligand-receptor combinations that could be exploited to transport molecules across the blood brain barrier (BBB). As reported in Wiley et al., researchers found that gold nanoparticles with moderate transferrin content were most effective at crossing the BBB into the brain parenchyma. The researchers proposed a mechanism underlying their observations. Nanoparticles with moderate transferrin content (I) engage the transferrin receptor on BBB endothelial cells, undergo receptor-mediated transcytosis to traverse the BBB and are then released into the brain parenchyma. Nanoparticles with high transferrin content (II) remain associated with BBB endothelial cells and fail to be released into the brain parenchyma after receptor-mediated transcytosis. On the other hand, nanoparticles with low transferrin content (III) fail to engage the transferrin receptor on BBB endothelial cells.