Novel histidine-conjugated galactosylated cationic liposomes for efficient hepatocyte-selective gene transfer in human hepatoma HepG2 cells
Novel histidine-conjugated galactosylated cationic liposomes for efficient hepatocyte-selective gene transfer in human hepatoma HepG2 cells
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DOI：
10.1016/j.jconrel.2006.12.019
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发表时间：
2007-04-02
影响因子：
10.8
通讯作者：
Hashida, Mitsuru
中科院分区：
文献类型：
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作者：
Shigeta, Kosuke;Kawakami, Shigeru;Hashida, Mitsuru
为了增强阳离子脂质体对肝细胞的基因转染，有必要克服从给药到基因表达过程中存在的一些障碍。最近，我们和其他研究小组已经证明质粒DNA (PDNA)/阳离子脂质体复合物（脂质体）从内体逃逸到细胞质是有速率限制的。本研究提出利用“质子海绵效应”，通过促进脂质体从核内体向细胞质的释放来提高转染效率。在这里，我们合成了一种新的ph敏感组氨酸修饰的半乳糖化胆固醇衍生物（Gal-His-C4-Chol），用于更有效地将基因传递到肝细胞。在HepG2细胞中，基于受体介导的机制，含有Gal-His-C4-Chol的脂质体比常规Gal-C4-Chol脂质体表现出更大的转染活性。因此，这一发现将有助于利用阳离子脂质体进行基因治疗的临床应用。(c) 2006 Elsevier B.V.版权所有
To enhance gene transfection to hepatocytes by cationic liposomes, it is necessary to overcome a number of barriers existing in the process from administration to gene expression. Recently we and other group have demonstrated that the escape of plasmid DNA (PDNA)/cationic liposome complexes (lipoplexes) from the endosome to cytoplasm was rate limiting. In this study, to enhance transfection efficiency by promoting the release of lipoplexes from the endosome to cytoplasm, we proposed utilizing the "proton sponge effect". Here, we synthesized a novel pH-sensitive histidine-modified galactosylated cholesterol derivative (Gal-His-C4-Chol), for a more efficient gene delivery to hepatocytes. Liposomes containing Gal-His-C4-Chol showed much greater transfection activity than conventional Gal-C4-Chol liposomes based on a receptor-mediated mechanism in HepG2 cells. Hence, this finding should contribute to the development of gene therapy using cationic liposomes toward their clinical application. (c) 2006 Elsevier B.V. All rights reserved.