Unraveling GLUT-mediated transcytosis pathway of glycosylated nanodisks  

作　　者：Huan Wang Zui Zhang Juan Guan Weiyue Lu Changyou Zhan 

机构地区：[1]Department of Pharmacology,School of Basic Medical Sciences and State Key Laboratory of Molecular Engineering of Polymers,Fudan University,Shanghai 200032,China [2]Center of Medical Research and Innovation,Shanghai Pudong Hospital,Fudan University Pudong Medical Center,Shanghai 201399,China [3]School of Pharmacy,Fudan University and Key Laboratory of Smart Drug Delivery(Fudan University),Ministry of Education and PLA,Shanghai 201203,China [4]State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science,Institutes of Brain Science,Fudan University,Shanghai 200032,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2021年第1期120-128,共9页亚洲药物制剂科学（英文）

基　　金：financially supported by the National Natural Science Foundation of China(81973245,81773657,81673361,81690263 and 81673370);China Postdoctoral Science Foundation(2019M651385);National Postdoctoral Program for Innovative Talent(BX20190086);Shanghai Municipal Commission of Health and Family Planning(2018BR04);Shanghai Natural Science Foundation(19431900300 and18ZR1404800);Pudong New Area Commission of Science&Technology(PKJ2016-Y46).

摘　　要：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.Gly-A7R-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.

关 键 词：Blood-brain barrier TRANSCYTOSIS Glucose transporter Glycosylation Lysosomal exocytosis 

分 类 号：R943[医药卫生—药剂学]