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Abstract
Recently, nanocarriers that transport bioactive substances to a target site in the body have attracted considerable attention and undergone rapid progression in terms of the state of the art. However, few nanocarriers can enter the brain via a systemic route through the blood-brain barrier (BBB) to efficiently reach neurons. Here we prepare a self-assembled supramolecular nanocarrier with a surface featuring properly configured glucose. The BBB crossing and brain accumulation of this nanocarrier are boosted by the rapid glycaemic increase after fasting and by the putative phenomenon of the highly expressed glucose transporter-1 (GLUT1) in brain capillary endothelial cells migrating from the luminal to the abluminal plasma membrane. The precisely controlled glucose density on the surface of the nanocarrier enables the regulation of its distribution within the brain, and thus is successfully optimized to increase the number of nanocarriers accumulating in neurons.
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1 Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
2 Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo, Japan; Center for Brain Integration Research, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo, Japan
3 Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
4 Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan; Department of Otorhinolaryngology and Head and Neck Surgery, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
5 Innovation Center of NanoMedicine, Kawasaki Institute of Industrial Promotion, Kawasaki-ku, Kawasaki, Japan
6 Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan; Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
7 Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Bunkyo-ku, Tokyo, Japan; Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
8 Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, Midori-ku, Yokohama, Japan
9 Department of Otorhinolaryngology and Head and Neck Surgery, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
10 Innovation Center of NanoMedicine, Kawasaki Institute of Industrial Promotion, Kawasaki-ku, Kawasaki, Japan; Policy Alternatives Research Institute, The University of Tokyo, Bunkyo-ku, Tokyo, Japan