Surface-modified LPD nanoparticles for tumor targeting

Surface-modified LPD nanoparticles for tumor targeting
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DOI:
10.1196/annals.1348.001
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发表时间:
2006-01-01
期刊:
OLIGONUCLEOTIDE THERAPEUTICS
影响因子:
--
通讯作者:
Huang, Leaf
Huang, Leaf
中科院分区:
其他
文献类型:
--
作者:
Li, Shyh-Dar;Huang, Leaf

文献摘要

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我们开发了一种用于 siRNA 的肿瘤靶向 LPD 制剂(脂质体-聚化-DNA 复合物)。通过表面修饰,靶向聚乙二醇化 LPD 将递送效率提高了四倍,将基因沉默效果提高了两到三倍。通过靶向 LPD 下调人肺癌细胞中的生存素可诱导 90% 的细胞凋亡,并使细胞对顺铂的敏感性提高四倍。聚乙二醇化 LPD 制剂还显着改善了 siRNA 在 NCI-H460 人肺癌异种移植模型中的肿瘤定位。肿瘤似乎是表面修饰 LPD 中配制的 siRNA 的主要摄取器官。我们令人鼓舞的结果表明,表面修饰的 LPD 可能是基于 RNAi 的肿瘤治疗的有效载体。
We have developed a tumor-targeted LPD formulation (liposome-polyeation-DNA complex) for siRNA. With surface modification, the targeted, PEGylated LPD increased the delivery efficiency by four-fold and the gene-silencing effect by two- to three-fold. Downregulation of survivin in human lung cancer cells by targeted LPD induced 90% of apoptosis and sensitized the cells to cisplatin by four-fold. PEGylated LPD formulation also significantly improved the tumor localization of siRNA in the NCI-H460 human lung cancer xenograft model. The tumor appeared to be the major uptake organ for siRNA formulated in surface-modified LPD. Our encouraging results indicate that surface-modified LPD may be a potent carrier for RNAi-based tumor therapy.