Novel intracellular delivery system of antisense oligonucleotide by self-assembled hybrid micelles composed of DNA/PEG conjugate and cationic fusogenic peptide
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作者:
Jeong, JH
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机构:Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea
Jeong, JH
Kim, SW
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机构:Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea
Kim, SW
Park, TG
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Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South KoreaKorea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea
Park, TG
[1
]
机构:
[1] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea
[2] Univ Utah, CCCD, Dept Pharmaceut & Pharmaceut Chem, Salt Lake City, UT 84112 USA
An antisense oligonucleotide (ODN), c-myb, was covalently conjugated to poly(ethylene glycol) (PEG) via an acid-cleavable phosphoramidate linkage to form a diblock copolymer-like structure. The phosphoramidate linkage between ODN and PEG was completely cleaved within 5 h in an endosomal acidic condition (pH 4.7). When complexed with a cationic fasogenic peptide, KALA, the ODN/PEG conjugate self-associated to form polyelectrolyte complex micelles in an aqueous solution. The anionic ODN segments were ionically interacted with cationic KALA peptide to form an inner polyelectrolyte complex core, while the PEG segments constituted a surrounding corona. Effective hydrodynamic volume of the micelles was ca. 70 nm with a very narrow size distribution. The polyelectrolyte complex micelles, composed of c-myb ODN-PEG conjugate and KALA, were transported into cells far more efficiently than c-myb ODN itself. They also exhibited higher antiproliferative activity against smooth muscle cells. This study demonstrates that the DNA/PEG hybrid micelles system can be applied for the delivery of antisense oligonucleotide.
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Leiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, NetherlandsLeiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, Netherlands
de Vrueh, RLA
Rump, ET
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Leiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, NetherlandsLeiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, Netherlands
Rump, ET
Sliedregt, LAJM
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Leiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, NetherlandsLeiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, Netherlands
Sliedregt, LAJM
Biessen, EAL
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Leiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, NetherlandsLeiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, Netherlands
Biessen, EAL
van Berkel, TJC
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Leiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, NetherlandsLeiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, Netherlands
van Berkel, TJC
Bijsterbosch, MK
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Leiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, NetherlandsLeiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, Netherlands
机构:
Leiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, NetherlandsLeiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, Netherlands
de Vrueh, RLA
Rump, ET
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Leiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, NetherlandsLeiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, Netherlands
Rump, ET
Sliedregt, LAJM
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Leiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, NetherlandsLeiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, Netherlands
Sliedregt, LAJM
Biessen, EAL
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Leiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, NetherlandsLeiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, Netherlands
Biessen, EAL
van Berkel, TJC
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Leiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, NetherlandsLeiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, Netherlands
van Berkel, TJC
Bijsterbosch, MK
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Leiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, NetherlandsLeiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, NL-2300 RA Leiden, Netherlands