論文 - 詳細
| RRC ID | 18505 |
|---|---|
| 著者 | Chang KL, Higuchi Y, Kawakami S, Yamashita F, Hashida M. |
| タイトル | Development of lysine-histidine dendron modified chitosan for improving transfection efficiency in HEK293 cells. |
| ジャーナル | J Control Release |
| Abstract |
Chitosan has potential as a biocompatible gene carrier. However, its gene transfection efficiency is low because of its slow endosomal escape rate. Histidine has buffering capacity in the pH range of endosomes/lysosomes. The structure of dendron consists of a central core with several chains radiating from it and many histidines could be conjugated on the surface, increasing the efficiency of histidine modification. The purpose of this study is to increase the gene transfection efficiency of chitosan by promoting its endosomal escape property. We developed fourth-generation lysine-histidine (KH) dendrons that can provide 8 histidines in one dendron molecule. Chitosan-dendron (Chi13k-D) was synthesized using 2-iminothiolane to form the linkage; this was confirmed by NMR and the ninhydrin test. The buffering range, as measured by pH titration, was broader in the Chi13k-D group than in chitosan. Enhanced endosomal escape of Chi13k-D/pDNA complexes was confirmed using fluorescence-labeled endosomes and pDNA. The intralysosomal pH of Chi13k-D/pDNA was also higher than that of chitosan/pDNA. The gene transfection efficiency of Chi13k-D/pDNA was higher than that of chitosan/pDNA in HEK293 cells. These results suggest that KH dendron modification could provide high buffering capacity, which would increase the gene transfection efficiency of chitosan. |
| 巻・号 | 156(2) |
| ページ | 195-202 |
| 公開日 | 2011-12-10 |
| DOI | 10.1016/j.jconrel.2011.07.021 |
| PII | S0168-3659(11)00500-1 |
| PMID | 21802461 |
| MeSH | Anthracenes / chemical synthesis Anthracenes / chemistry* Chitosan / chemical synthesis Chitosan / chemistry* DNA / administration & dosage* HEK293 Cells Histidine / chemical synthesis Histidine / chemistry* Humans Hydrogen-Ion Concentration Lysine / chemical synthesis Lysine / chemistry* Plasmids / administration & dosage Transfection* |
| IF | 7.727 |
| 引用数 | 34 |
| WOS 分野 | PHARMACOLOGY & PHARMACY CHEMISTRY, MULTIDISCIPLINARY |
| 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 | 4 |
| 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 | 293(RCB1637) |