Multivalent display of oligosaccharides on nanoparticles accelerates their nuclear import

Abstract

335Trends in Glycoscience and Glycotechnology Vol. 21 No. 122 (2009) AbstractIt has been reported that the conjugation of carbohydrate to proteins can promote the nuclear import of proteins (1-4). In this minireview, based on our recent data, we discuss the eŠect of carbohydrates on the nuclear import using quantum dots (QDs), with particular reference to the manner in which the chemical structure and density of carbohydrates displayed on their surface drastically aŠected the e‹ciency of QD permeation into the nucleus. Among the carbohydrates used in our study, the high-density display of maltotriose was the most e‹cient for the nuclear import of QDs. As it is not reliant on cytosolic factors for nuclear import, we concluded that the sugar-displaying QDs can be transported into the nucleus via passive diŠusion rather than through a speciˆc receptor-mediated pathway.A. Importance of nuclear import and nuclear localization signals Cytosol-nuclear transportation is the most common form of tra‹c within cells. The nuclear pore complexes (NPCs) form channels penetrating the double lipid bilayer of the nuclear envelope, and, in nature, the nuclear import of histones and transcriptional factors, and the nuclear export of ribosomes and various RNA occurs through these nuclear pores (5,6). Thus, the study of transportation through nuclear pores is meaningful both as basic biology and for its application to the development of drug delivery systems (DDSs) and bioimaging. With regard to DDSs, many researchers have explored the entrance to the plasma membrane and its subsequent release from the lysosome (7-9); however, few studies have targeted nuclear import. We have focused on the nuclear transportation of nanoparticles due to its wide range of applications, such as DDS and molecular imaging. The entrance

Nuclear transport facilitated by the interaction between nuclear pores and carbohydrates

“…We have reported that maltotriose (Glc 3 : three glucose units)-displaying quantum dots (Glc 3 -QDs) easily diffuse into the nucleus in digitonin-permeabilized cells. 26,27 We aim to clarify how the maltooligosaccharide modification of nanoparticles allows rapid passage through the NPC barrier and then optimize the nuclear import of QDs through the modulation of the length of the attached oligosaccharide. We prepared maltooligo-QDs, in which the length of the oligosaccharide varied from 1 to 7 glucose units (Glc 1 , Glc 3 , Glc 5 and Glc 7 ) (Scheme 1).…”