Abstract
Nano-structured systems have been attracting attention as carriers that can selectively transport bioactive substances such as nucleic acid medicine to a target location in the body. However, none of these systems have been able to cross the blood-brain barrier （BBB） via a systemic route to realize safe and efficient delivery of their cargo to the brain parenchyma. To tackle this problem, the authors focused on a transport protein, glucose transporter-1（GLUT1）, which is highly expressed in brain capillary endothelial cells （BCECs）, to facilitate the transport of nano-structured systems across the BBB. GLUT1 is known to migrate from the luminal side to the abluminal side in response to a rapid increase of blood glucose concentration from the hypoglycemic state. Utilizing such unique characteristic of GLUT1, the authors designed a self-assembled supramolecular nanocarrier with glucose integrated on the surface at an optimal configuration. Results obtained in vivo have shown significant accumulation of the nanocarrier within the brain parenchyma, at an efficiency that far surpasses that of conventional strategies. Precise control of glucose density on the surface of the nanocarrier allowed selection of the accumulation point in the brain, and a particularly high degree of accumulation in the neurocytes was achieved. The developed method can be used for efficiently delivering a variety of drug modalities to the brain, which offers new treatment strategies to cure neurological disorders such as the Alzheimer’s disease.
