論文 - 詳細
| RRC ID | 43786 |
|---|---|
| 著者 | Hayashi Y, Mori Y, Yamashita S, Motoyama K, Higashi T, Jono H, Ando Y, Arima H. |
| タイトル | Potential use of lactosylated dendrimer (G3)/α-cyclodextrin conjugates as hepatocyte-specific siRNA carriers for the treatment of familial amyloidotic polyneuropathy. |
| ジャーナル | Mol Pharm |
| Abstract |
To reveal the potential use of lactosylated-dendrimer (G3) conjugates with α-cyclodextrin (Lac-α-CDE (G3)) as novel hepatocyte-specific siRNA carriers in order to treat transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP), we evaluated the RNAi effect of siRNA complexes with Lac-α-CDE (G3) both in vitro and in vivo. Herein, we targeted TTR gene expression because TTR-related FAP was often caused by amyloidogenic TTR (ATTR), which mainly expresses in hepatocytes. Lac-α-CDE (G3, average degree of substitution of lactose (DSL) 1.2)/siRNA complex had a potent RNAi effect against TTR gene expression through adequate physicochemical properties, asialoglycoprotein receptor (ASGP-R)-mediated cellular uptake, efficient endosomal escape and the delivery of the siRNA complex to cytoplasm, but not nucleus, with negligible cytotoxicity. Lac-α-CDE (G3, DSL 1.2)/siRNA complex had the potential to induce the in vivo RNAi effect after intravenous administration in the liver of mice. The blood chemistry values in the α-CDE (G3) and Lac-α-CDE (G3, DSL 1.2) systems were almost equivalent to those in the control system (5% mannitol solution). Taken together, these results suggest that Lac-α-CDE (G3, DSL 1.2) has the potential for a novel hepatocyte-selective siRNA carrier in vitro and in vivo, and has a possibility as a therapeutic tool for FAP to the liver transplantation. |
| 巻・号 | 9(6) |
| ページ | 1645-53 |
| 公開日 | 2012-6-4 |
| DOI | 10.1021/mp200654g |
| PMID | 22510029 |
| MeSH | Amyloid Neuropathies, Familial / metabolism Amyloid Neuropathies, Familial / therapy* Animals Blotting, Western Dendrimers / chemistry* Flow Cytometry Genetic Vectors / administration & dosage Genetic Vectors / chemistry* Hep G2 Cells Hepatocytes / metabolism* Humans Lactose / chemistry* Male Mice Microscopy, Fluorescence Prealbumin / genetics Prealbumin / metabolism RNA, Small Interfering / administration & dosage* RNA, Small Interfering / genetics* Real-Time Polymerase Chain Reaction alpha-Cyclodextrins / chemistry* |
| IF | 4.321 |
| 引用数 | 40 |
| WOS 分野 | PHARMACOLOGY & PHARMACY MEDICINE, RESEARCH & EXPERIMENTAL |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 7 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Hep G2 |