Transferrin-appended β-(1→3)-D-glucan schizophyllan for antisense oligonucleotides delivery to enhance the cellular uptake

Abstract

Schizophyllan (SPG) is a natural β-(1→3)-D-glucan existing as a triple helix in water and as a single chain in dimethylsulfoxide (DMSO), respectively. As we already reported, when a homo-phosphodiester polynucleotide [for example, poly(dA) or poly(C)] is added to the SPG/DMSO solution and subsequently DMSO is exchanged for water, SPG forms a complex with the polynucleotide. One of the potential applications of this novel complex is an antisense-oligonucleotide (AS ODN) carrier. The present paper describes a modification technique which enables us to introduce transferrin to the reducing end of SPG (Tf-SPG). We made a complex from Tf-SPG and AS ODN and carried out an in vitro antisense assay. We found that Tf-SPG dramatically enhances the antisense effect. Their superiority can be ascribed to enhancement of endocytosis due to the attached transferrin. One of the peculiar features of our system is that the complex (i.e., carrier + AS ODN) is charged negatively in total, because SPG itself is a neutral polysaccharide. This feature is different from the conventional systems such as cationic liposomes and polycations. The present work has thus clarified that SPG can act as a new potential candidate for AS ODN carriers. [DOI: 10.1380/ejssnt.2005.195]