Unraveling GLUT-mediated transcytosis pathway of glycosylated nanodisks

Glucose transporter (GLUT)-mediated transcytosis has been validated as an efficient method to cross the blood-brain barrier and enhance brain transport of nanomedicines. However, the transcytosis process remains elusive. Glycopeptide-modified nanodisks (Gly-A7R-NDs), which demonstrated high capacity of brain targeting via GLUT-mediated transcytosis in our previous reports, were utilized to better understand the whole transcytosis process. GlyA7R-NDs internalized brain capillary endothelial cells mainly via GLUT-mediated/clathrin dependent endocytosis and macropinocytosis. The intracellular Gly-A7R-NDs remained intact, and the main excretion route of Gly-A7R-NDs was lysosomal exocytosis. Glycosylation of nanomedicine was crucial in GLUT-mediated transcytosis, while morphology did not affect the efficiency. This study highlights the pivotal roles of lysosomal exocytosis in the process of GLUT-mediated transcytosis, providing a new impetus to development of brain targeting drug delivery by accelerating lysosomal exocytosis. (c) 2020 Shenyang Pharmaceutical University. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Automated summary

This study investigates the process of GLUT-mediated transcytosis using Glycopeptide-modified nanodisks (Gly-A7R-NDs), revealing the crucial role of lysosomal exocytosis in this process and providing new insights for the development of brain targeting drug delivery.