Effect of cholesterol nanodomains on the targeting of lipid-based gene delivery in cultured cells.
Effect of cholesterol nanodomains on the targeting of lipid-based gene delivery in cultured cells.
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DOI：
10.1021/mp100097b
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发表时间：
2010-08-02
影响因子：
4.9
通讯作者：
Anchordoquy TJ
中科院分区：
文献类型：
--
作者：
Xu L;Anchordoquy TJ
靶向基因传递为临床应用提供了巨大的潜力。靶向配体修饰的脂质体已广泛用于体内和体外基因传递。高胆固醇含量的脂丛导致复合物内胆固醇结构域的形成，已显示出体外转染增强和对血清诱导聚集的抗性。在本研究中，叶酸被用作靶向配体，与胆固醇或二酰基脂质（DSPE）偶联，并将这些偶联物纳入已知具有胆固醇纳米结构域的DOTAP/胆固醇配制的脂质体（wt/wt: 31/69）。当配体位于胆固醇纳米结构域内或排除在胆固醇纳米结构域外时，研究了在50%血清存在下这些脂丛的细胞摄取和转染。与叶酸- dspe相比，叶酸-胆固醇脂质体转染量增加了50倍，而细胞摄取水平仅为叶酸- dspe的40%。这些结果表明，胆固醇结构域内配体的存在促进了培养细胞中更高效的转染，并且脂丛进入细胞后的细胞内运输在基因传递中起着至关重要的作用。
Targeted gene delivery offers immense potential for clinical applications. Liposomes decorated with targeting ligands have been extensively used for both in vitro and in vivo gene delivery. Lipoplexes with high cholesterol content that result in cholesterol domain formation within the complexes have been shown to exhibit enhanced transfection in vitro and resistance to serum-induced aggregation. In the present study, folate was employed as a targeting ligand that was conjugated with either cholesterol or a diacyl lipid (DSPE), and these conjugates were incorporated into lipoplexes formulated with DOTAP/cholesterol (wt/wt: 31/69) that are known to possess cholesterol nanodomains. Cellular uptake and transfection of these lipoplexes in the presence of 50% serum were examined when the ligand is located within or excluded from the cholesterol nanodomain. Lipoplexes with folate-cholesterol exhibited a 50-fold increase in transfection as compared to those with folate-DSPE, while the cellular uptake level is only 40% of that with folate-DSPE. These results indicate that the presence of the ligand within the cholesterol domain promotes more productive transfection in cultured cells, and intracellular trafficking of the lipoplexes after entry into cells plays a crucial role in gene delivery.
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影响因子：
5.1
作者：
Li, S;Tseng, WC;Huang, L
通讯作者：
Huang, L
影响因子：
5.1
作者：
Tam, P;Monck, M;Cullis, PR
通讯作者：
Cullis, PR
影响因子：
10.8
作者：
Li, Shyh-Dar;Chono, Sumio;Huang, Leaf
通讯作者：
Huang, Leaf
影响因子：
4.7
作者：
Cheng, Han;Zhu, Jing-Ling;Zhuo, Ren-Xi
通讯作者：
Zhuo, Ren-Xi
DOI：
10.1073/pnas.85.18.6949
发表时间：
1988-09-01
影响因子：
11.1
作者：
GABIZON, A;PAPAHADJOPOULOS, D
通讯作者：
PAPAHADJOPOULOS, D