%0 Journal Article %A Takahashi, Yosuke %A Araie, Yuki %A Nomura, Daiki %A Takahashi, Yuki %A Sano, Kohei %A Saji, Hideo %A Takakura, Yoshinobu %A Nishikawa, Makiya %D 2017 %T Construction of nanostructured DNA harbouring phosphorodiamidate morpholino oligonucleotide for controlled tissue distribution in mice %U https://tandf.figshare.com/articles/journal_contribution/Construction_of_nanostructured_DNA_harbouring_phosphorodiamidate_morpholino_oligonucleotide_for_controlled_tissue_distribution_in_mice/5509444 %R 10.6084/m9.figshare.5509444.v1 %2 https://tandf.figshare.com/ndownloader/files/9536836 %K Word %K drug targeting %K nanotechnology %K oligodeoxynucleotides (ODNs) %K pharmacokinetics %K targeted drug delivery %X

Phosphorodiamidate morpholino oligonucleotides (PMOs) are a class of antisense oligonucleotides used in the treatment of neuromuscular diseases. Their major drawbacks are high blood clearance and poor cellular delivery. Previously, we demonstrated that tripod-like nanostructured DNA, or tripodna, was efficiently taken up by macrophages and dendritic cells. In this study, we used iodine-125(125I)-labelled PMOs, designed a tripodna harbouring an 125I-PMO (125I-PMO/tripodna), and evaluated whether this tripodna could control the pharmacokinetic properties of PMO. Gel electrophoresis showed that 125I-PMO was almost completely incorporated into the tripodna. Compared to 125I-PMO, 125I-PMO/tripodna was more efficiently taken up by macrophage-like RAW264.7 cells. Moreover, after intravenous injection into mice, the area under the plasma concentration–time curve of 125I-PMO/tripodna was significantly larger than that of 125I-PMO. The distribution of 125I-PMO/tripodna in the liver and spleen at 24 h was 32- and 51-fold higher than that of 125I-PMO, respectively. The fractionation of liver cells revealed that non-parenchymal cells were the major cells contributing to the hepatic uptake of 125I-PMO/tripodna. These results indicate that tripodna has the potential to deliver PMO, particularly to the liver and spleen.

%I Taylor & Francis