Glycaemic control boosts glucosylated nanocarrier crossing the BBB into the brain

作者：Yasutaka Anraku, Hiroya Kuwahara, Yu Fukusato, Asao Mizoguchi, T. Ishii, Keiko Nitta, Yu Matsumoto, Kazuko Toh, Kanjiro Miyata, Satoshi Uchida, Kazutaka Nishina, Kensuke Osada, Keiji Itaka, Nobuhiro Nishiyama, Hidehiro Mizusawa, Tatsuya Yamasoba, Takanori Yokota, Kazunori Kataoka · 发表于：Nature Communications · 年份：2017 · DOI：10.1038/s41467-017-00952-3 · 被引用次数：297 · 研究领域：Supramolecular Self-Assembly in Materials、Nanoparticle-Based Drug Delivery、Supramolecular Chemistry and Complexes

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.There are only a few examples of nanocarriers that can transport bioactive substances across the blood-brain barrier. Here the authors show that by rapid glycaemic increase the accumulation of a glucosylated nanocarrier in the brain can be controlled.