Construction of nanostructured DNA harbouring phosphorodiamidate morpholino oligonucleotide for controlled tissue distribution in mice
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.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2018 |
---|---|
Erschienen: |
2018 |
Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
---|---|
Enthalten in: |
Journal of drug targeting - 26(2018), 4 vom: 25. Apr., Seite 373-381 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Takahashi, Yosuke [VerfasserIn] |
---|
Links: |
---|
Anmerkungen: |
Date Completed 16.07.2019 Date Revised 16.07.2019 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1080/1061186X.2017.1387789 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM276424573 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM276424573 | ||
003 | DE-627 | ||
005 | 20231225011955.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231225s2018 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1080/1061186X.2017.1387789 |2 doi | |
028 | 5 | 2 | |a pubmed24n0921.xml |
035 | |a (DE-627)NLM276424573 | ||
035 | |a (NLM)28972806 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Takahashi, Yosuke |e verfasserin |4 aut | |
245 | 1 | 0 | |a Construction of nanostructured DNA harbouring phosphorodiamidate morpholino oligonucleotide for controlled tissue distribution in mice |
264 | 1 | |c 2018 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 16.07.2019 | ||
500 | |a Date Revised 16.07.2019 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a 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 | ||
650 | 4 | |a Comparative Study | |
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a Word | |
650 | 4 | |a drug targeting | |
650 | 4 | |a nanotechnology | |
650 | 4 | |a oligodeoxynucleotides (ODNs) | |
650 | 4 | |a pharmacokinetics | |
650 | 4 | |a targeted drug delivery | |
650 | 7 | |a Iodine Radioisotopes |2 NLM | |
650 | 7 | |a Morpholinos |2 NLM | |
650 | 7 | |a Oligonucleotides, Antisense |2 NLM | |
650 | 7 | |a DNA |2 NLM | |
650 | 7 | |a 9007-49-2 |2 NLM | |
650 | 7 | |a Iodine-125 |2 NLM | |
650 | 7 | |a GVO776611R |2 NLM | |
700 | 1 | |a Araie, Yuki |e verfasserin |4 aut | |
700 | 1 | |a Nomura, Daiki |e verfasserin |4 aut | |
700 | 1 | |a Takahashi, Yuki |e verfasserin |4 aut | |
700 | 1 | |a Sano, Kohei |e verfasserin |4 aut | |
700 | 1 | |a Saji, Hideo |e verfasserin |4 aut | |
700 | 1 | |a Takakura, Yoshinobu |e verfasserin |4 aut | |
700 | 1 | |a Nishikawa, Makiya |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Journal of drug targeting |d 1996 |g 26(2018), 4 vom: 25. Apr., Seite 373-381 |w (DE-627)NLM074733958 |x 1029-2330 |7 nnns |
773 | 1 | 8 | |g volume:26 |g year:2018 |g number:4 |g day:25 |g month:04 |g pages:373-381 |
856 | 4 | 0 | |u http://dx.doi.org/10.1080/1061186X.2017.1387789 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 26 |j 2018 |e 4 |b 25 |c 04 |h 373-381 |