Legumain-induced intracerebrally crosslinked vesicles for suppressing efflux transport of Alzheimer’s disease multi-drug nanosystem  

作　　者：Fuxin Jiang Jian Ren Yachai Gao Jinna Wang Yiping Zhao Fengying Dai 

机构地区：[1]School of Material Science and Engineering,Tianjin Key Laboratory of Separation Membranes and Membrane Processes,National Center for International Joint Research on Separation Membranes,Tiangong University,Tianjin,300387,China

出　　处：《Bioactive Materials》2021年第6期1750-1764,共15页生物活性材料（英文）

基　　金：This work was financially sponsored by the National Natural Science Foundation of China(Nos.51773152);the Science and Technology Plans of Tianjin(15JCYBJC17900);the Natural Science Foundation of Tianjin(18JCYBJC17500).

摘　　要：Brain barrier is both a protective permeability hurdle and a limitation site where therapeutic agents are excluded to enter the target region.Designing drug vehicle to overcome this notorious barrier bottle is challenging.Herein,we construct a stimuli-responsive self-assembled nanovesicle that delivers water-soluble drugs to prevent the efflux transport of brain barriers by responding to the endogenously occurring signals in Alzheimer’s disease(AD)brain microenvironment.Once stimuli-responsive vesicles are accumulated in intracerebrally,the intrinsically occurring legumain endopeptidase cleaves the Ac-Ala-Ala-Asn-Cys-Asp(AK)short peptide on the drug vesicles to expose the 1,2 thiol amino group to cyclize with the cyano groups on 2-cyano-6-aminobenzothiazole(CABT)of the chaperone vesicles,thus triggering the formation of cross-linked micrometre-scale vesicles.Such a structural alteration completely prevents further brain barriers efflux.The superior neuroprotective capacity of cross-linked vesicles is validated in senescence accelerated mouse prone 8(SAMP8).This smart multi-drug delivery vesicle is promising to serve as a powerful system for AD treatment and can be adapted for the therapy of other central nervous system(CNS)disorders.

关 键 词：LEGUMAIN Brain barrier Efflux transport Multi-drug delivery Alzheimer’s disease 

分 类 号：R318[医药卫生—生物医学工程]