A D‐Peptide Ligand of Nicotine Acetylcholine Receptors for Brain‐Targeted Drug Delivery1. (19th January 2015)

• Record Type: Journal Article
• Authors: Wei, Xiaoli; Zhan, Changyou; Shen, Qing; Fu, Wei; Xie, Cao; Gao, Jie; Peng, Chunmei; Zheng, Ping; Lu, Weiyue
• Is Part Of: Angewandte Chemie. Volume 127:Number 10(2015)
• Page Start: 3066
• Page End: 3070
• Publication Date: 2015-01-19
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201411226
• Languages: English
• ISSNs: 0044-8249

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Lysosomes of brain capillary endothelial cells are implicated in nicotine acetylcholine receptor (nAChR)‐mediated transcytosis and act as an enzymatic barrier for the transport of peptide ligands to the brain. A <sc>D</sc>‐peptide ligand of nAChRs (termed ^DCDX), which binds to nAChRs with an IC₅₀ value of 84.5 n<sc>M</sc>, was developed by retro–inverso isomerization. ^DCDX displayed exceptional stability in lysosomal homogenate and serum, and demonstrated significantly higher transcytosis efficiency in an in vitro blood–brain barrier monolayer compared with the parent <sc>L</sc>‐peptide. When modified on liposomal surface, ^DCDX facilitated significant brain‐targeted delivery of liposomes. As a result, brain‐targeted delivery of ^DCDX modified liposomes enhanced therapeutic efficiency of encapsulated doxorubicin for glioblastoma. This study illustrates the importance of ligand stability in nAChRs‐mediated transcytosis, and paves the way for developing stable brain‐targeted entities.</p> </abstract>