Lactosylated poly(ethylene glycol)-siRNA conjugate through acid-labile ß-thiopropionate linkage to construct pH-sensitive polyion complex micelles achieving enhanced gene silencing in hepatoma cells
Lactosylated poly(ethylene glycol)-siRNA conjugate through acid-labile ß-thiopropionate linkage to construct pH-sensitive polyion complex micelles achieving enhanced gene silencing in hepatoma cells
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DOI：
10.1021/ja044941d
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发表时间：
2005-02-16
影响因子：
15
通讯作者：
Kataoka, K
中科院分区：
文献类型：
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作者：
Oishi, M;Nagasaki, Y;Kataoka, K
通过与聚L-赖氨酸的混合，将含有酸不稳定的−-硫代丙酸键的乳糖化聚乙二醇化βsiRNA偶联物组装成多离子复合体胶束，显著增强了肝癌细胞中的基因沉默。PIC胶束的外围带有簇状乳糖部分，通过受体介导的方式成功地转移到肝癌细胞中，释放数百个活性的siRNA分子到细胞内部，响应内膜间隙的pH下降。最终，与游离结合物相比，胶束系统的基因沉默活性几乎提高了100倍，促进了siRNA疗法的实际应用。
The remarkably enhanced gene silencing in hepatoma cells was achieved by assembling lactosylated-PEG−siRNA conjugates bearing acid-labile β-thiopropionate linkages into polyion complex (PIC) micelles through the mixing with poly(l-lysine). The PIC micelles with clustered lactose moieties on the periphery were successfully transported into hepatoma cells in a receptor-mediated manner, releasing hundreds of active siRNA molecules into the cellular interior responding to the pH decrease in the endosomal compartment. Eventually, almost 100 times enhancement in gene silencing activity compared to that of the free conjugate was achieved for the micelle system, facilitating the practical utility of siRNA therapeutics.