Structure-function relationships of branched and linear β-1,3-glucan/DNA complexes in Dectin-1 recognition and nucleic acid delivery.

β-1,3-glucans (BGs) are promising biomaterials for targeted nucleic acid delivery because they can form stable complexes with single-stranded homopolynucleotides and interact with the C-type lectin receptor Dectin-1. However, the influence of structural differences among BGs on complex formation and receptor recognition remains poorly understood. Therefore, in this study, we compared complex formation behavior, structural characteristics, and CpG-ODN delivery efficiency between a β-1,6-branched BG, schizophyllan (SPG), and a linear β-1,3-glucan, curdlan (CUR). The model DNAs were a 40-mer poly(deoxyadenosine) single-stranded DNA (dA40), and CpG-ODN conjugated to the 5' end of dA40. Although both BGs formed stable complexes with dA40, their supramolecular structures differed, reflecting structural differences between branched and linear glucans. Both complexes retained Dectin-1 recognition; however, their binding ability differed between the SPG/dA40 and CUR/dA40 complexes. Cellular assays demonstrated efficient internalization in Dectin-1-expressing cells, and both BG/CpG complexes induced significantly more potent immune responses than naked CpG-ODNs. Despite their different binding abilities toward Dectin-1, both complexes induced similar levels of IL-6 and TNF-α, showing that stronger receptor recognition does not necessarily lead to greater immunostimulatory activity. These findings demonstrate that BG structural properties control complex formation and receptor interactions, providing mechanistic insights into the rational design of polysaccharide-based nucleic acid delivery systems.