Targeting delivery oligonucleotide into macrophages by cationic polysaccharide from Bletilla striata successfully inhibited the expression of TNF-α

Abstract

Competent vehicles based on natural biopolymers are highly demanded in the practice of gene-assisted cell therapy. In this study, a novel gene carrier was developed based on a bioactive glucomannan that was a polysaccharide isolated from an herb Bletilla striata (BSP) and modified with N, N′-carbonyldiimidazole (CDI)/ethylenediamine in order to acquire nucleic acid binding affinity. Particle size observation and electrophoretic mobility tests indicated that the cationized BSP (cBSP) could efficiently combine DNA to form nano-scaled compact and stable complexes and promote the transfection of oligodeoxynucleotide (ODN). Specifically, cBSP exhibited significantly high affinity to macrophages, as evidenced by transfection examination on multiple cell types and competitive test with mannose/glucomannan. In addition, the efficacy of the delivered ODN by cBSP was evaluated by the quantification of gene expression and a dramatic enhancement in suppressing target gene expression was observed. All the findings suggested the possible existence of interaction between cBSP ligand and receptor on macrophage surface. In this way, the ubiquitous mannose receptors and β-glucan receptors on macrophage could recognize the mannose and β-glucose residues in BSP framework, thus further mediated the oriented ODN delivery. We expect cBSP to be capable of conveying antisense nucleotides (e.g., oligodeoxynucleotide and small interference RNA) for the practical anti-inflammatory therapy. © 2008 Elsevier B.V. All rights reserved.