Jeong Ji Hoon, Kim Sun Hwa, Kim Sung Wan, Park Tae Gwan
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
J Nanosci Nanotechnol. 2006 Sep-Oct;6(9-10):2790-5. doi: 10.1166/jnn.2006.414.
A polyelectrolyte complex (PEC) micelle-based antisense oligodeoxynucleotide (ODN) delivery system was designed to overcome intrinsic limitations of cationic lipid-mediated gene transfer. Cationic lipid (Lipofectamine, LF) and ODN conjugated poly(ethylene glycol) (PEG) were ionically complexed to form self-assembled spherical PEC micelles. They have a distinctive structural feature: a charge-neutralized core surrounded by highly flexible PEG corona. The PEC micelles could be visualized as a nano-sized sphere by atomic force microscopy (AFM). The DNA/LF PEC micelles exhibited far improved transfection efficiency compared to those of conventional lipoplex formulations (ODN/LF) in the presence of serum. They showed enhanced cellular uptake followed by rapid nuclear localization of ODN in human epithelial carcinoma (KB) cells. In addition, anti-proliferative activity of c-raf gene-directed antisense ODN was almost fully maintained in KB cells in the presence of serum.
设计了一种基于聚电解质复合物（PEC）胶束的反义寡脱氧核苷酸（ODN）递送系统，以克服阳离子脂质介导的基因转移的内在局限性。阳离子脂质（Lipofectamine，LF）与ODN共轭聚乙二醇（PEG）进行离子复合，形成自组装球形PEC胶束。它们具有独特的结构特征：电荷中和的核心被高度柔性的PEG冠层包围。通过原子力显微镜（AFM）可将PEC胶束视为纳米级球体。在血清存在的情况下，与传统脂质体配方（ODN/LF）相比，DNA/LF PEC胶束表现出远更高的转染效率。它们显示出增强的细胞摄取，随后ODN在人上皮癌（KB）细胞中快速核定位。此外，在血清存在的情况下，c-raf基因导向的反义ODN在KB细胞中的抗增殖活性几乎完全得以维持。
