論文 - 詳細
| RRC ID | 44001 |
|---|---|
| 著者 | Arima H, Yoshimatsu A, Ikeda H, Ohyama A, Motoyama K, Higashi T, Tsuchiya A, Niidome T, Katayama Y, Hattori K, Takeuchi T. |
| タイトル | Folate-PEG-appended dendrimer conjugate with α-cyclodextrin as a novel cancer cell-selective siRNA delivery carrier. |
| ジャーナル | Mol Pharm |
| Abstract |
We previously reported that of the various polyamidoamine (PAMAM) STARBURST dendrimer (generation 3, G3) (dendrimer) conjugates with cyclodextrins (CyDs), the dendrimer (G3) conjugate with α-CyD having an average degree of substitution of 2.4 (α-CDE (G3)) has the greatest potential for a novel carrier for siRNA in vitro and in vivo. To improve the siRNA transfer activity and the lack of target specificity of α-CDE (G3), we prepared folate-polyethylene glycol (PEG)-appended α-CDEs (G3) (Fol-PαCs) with various degrees of substitution of folate (DSF) and evaluated their siRNA transfer activity to folate receptor (FR)-overexpressing cancer cells in vitro and in vivo. Of the three Fol-PαCs (G3, DSF 2, 4 and 7), Fol-PαC (G3, DSF 4) had the highest siRNA transfer activity in KB cells (FR-positive). Fol-PαC (G3, DSF 4) was endocytosed into KB cells through FR. No cytotoxicity of the siRNA complex with Fol-PαC (G3, DSF 4) was observed in KB cells (FR-positive) or A549 cells (FR-negative) up to the charge ratio of 100/1 (carrier/siRNA). In addition, the siRNA complex with Fol-PαC (G3, DSF 4) showed neither interferon response nor inflammatory response. Importantly, the siRNA complex with Fol-PαC (G3, DSF 4) tended to show the in vivo RNAi effects after intratumoral injection and intravenous injection in tumor cells-bearing mice. The FITC-labeled siRNA and TRITC-labeled Fol-PαC (G3, DSF 4) were actually accumulated in tumor tissues after intravenous injection in the mice. In conclusion, the present results suggest that Fol-PαC (G3, DSF 4) could potentially be used as a FR-overexpressing cancer cell-selective siRNA delivery carrier in vitro and in vivo. |
| 巻・号 | 9(9) |
| ページ | 2591-604 |
| 公開日 | 2012-9-4 |
| DOI | 10.1021/mp300188f |
| PMID | 22873579 |
| MeSH | Animals Cell Line, Tumor Dendrimers / administration & dosage Dendrimers / chemistry* Folic Acid / administration & dosage Folic Acid / chemistry* Gene Transfer Techniques* Humans Inflammation / genetics Inflammation / metabolism Interferons / genetics Interferons / metabolism KB Cells Male Mice Mice, Inbred BALB C Polyethylene Glycols / administration & dosage Polyethylene Glycols / chemistry* RNA, Small Interfering / administration & dosage* RNA, Small Interfering / genetics* alpha-Cyclodextrins / administration & dosage alpha-Cyclodextrins / chemistry* |
| IF | 4.321 |
| 引用数 | 68 |
| 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 | 2 |
| 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 | Colon-26(RCB2657) |