Jump to main content
Jump to site search

Issue 21, 2010
Previous Article Next Article

Design, synthesis and biological evaluation of carbohydrate-functionalized cyclodextrins and liposomes for hepatocyte-specific targeting

Author affiliations

Abstract

Targeting glycan-binding receptors is an attractive strategy for cell-specific drug and gene delivery. The C-type lectin asialoglycoprotein receptor (ASGPR) is particularly suitable for liver-specific delivery due to its exclusive expression by parenchymal hepatocytes. In this study, we designed and developed an efficient synthesis of carbohydrate-functionalized β-cyclodextrins (βCDs) and liposomes for hepatocyte-specific delivery. For targeting of ASGPR, rhodamine B-loaded βCDs were functionalized with glycodendrimers. Liposomes were equipped with synthetic glycolipids containing a terminal D-GalNAc residue to mediate binding to ASGPR. Uptake studies in the human hepatocellular carcinoma cell line HepG2 demonstrated that βCDs and liposomes displaying terminal D-Gal/D-GalNAc residues were preferentially endocytosed. In contrast, uptake of βCDs and liposomes with terminal D-Man or D-GlcNAc residues was markedly reduced. The D-Gal/D-GalNAc-functionalized βCDs and liposomes presented here enable hepatocyte-specific targeting. Gal-functionalized βCDs are efficient molecular carriers to deliver doxorubicin in vitro into hepatocytes and induce apoptosis.

Graphical abstract: Design, synthesis and biological evaluation of carbohydrate-functionalized cyclodextrins and liposomes for hepatocyte-specific targeting

Back to tab navigation

Supplementary files

Article information


Submitted
02 Jul 2010
Accepted
22 Jul 2010
First published
02 Sep 2010

Org. Biomol. Chem., 2010,8, 4987-4996
Article type
Paper

Design, synthesis and biological evaluation of carbohydrate-functionalized cyclodextrins and liposomes for hepatocyte-specific targeting

G. J. L. Bernardes, R. Kikkeri, M. Maglinao, P. Laurino, M. Collot, S. Y. Hong, B. Lepenies and P. H. Seeberger, Org. Biomol. Chem., 2010, 8, 4987
DOI: 10.1039/C0OB00372G

Social activity

Search articles by author

Spotlight

Advertisements