Formation of DNA nanotubes increases uptake into fibroblasts via enhanced affinity for collagen

DNA nanostructures are promising delivery carriers because of their flexible structural design and high biocompatibility. Selectivity in cellular uptake is an important factor in the development of DNA-nanostructure-based delivery carriers. In this study, DNA nanotubes were selected as the DNA structures, and their selectivity for cellular uptake and the mechanisms involved were investigated. Unlike DNA nanostructures such as polypod-like nanostructured DNA or DNA tetrahedrons, which are easily taken up by macrophages, the formation of DNA nanotubes increases uptake by fibroblasts and fibroblast-like cells. We focused on the collagen expressed in cells as a factor in this process, and found DNA nanotube formation increased the affinity for type I collagen compared with that of single-stranded DNA. Collagenase treatment removes collagen from fibroblasts and reduces the uptake of DNA nanotubes by fibroblasts. We directly observed DNA nanotube uptake by fibroblasts using transmission electron microscopy, whereby the nanotubes were distributed on the cell surface, folded, frag-mented, and taken up by phagocytosis. In conclusion, we demonstrated a novel finding that DNA nanotubes are readily taken up by fibroblasts and myoblasts.