Novel intracellular delivery system of antisense oligonucleotide by self-assembled hybrid micelles composed of DNA/PEG conjugate and cationic fusogenic peptide

被引:145
作者
Jeong, JH
Kim, SW
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
关键词
D O I
10.1021/bc025632k
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:473 / 479
页数:7
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