論文 - 詳細
| RRC ID | 11190 |
|---|---|
| 著者 | Horiuchi S, Aoyama Y. |
| タイトル | Systematic lactose-functionalization of amphiphilic octaamine macrocycle as a gene carrier. Optimization of the charge, size, toxicity, and receptor factors for hepatocyte targeting. |
| ジャーナル | J Control Release |
| Abstract |
We investigated the transfection properties of singly and triply lactose-functionalized derivatives, Lac(1) and Lac(3), and non-glycosylated one, Lac(0), of calix[4]resorcarene-based amphiphilic octaamine 1 in light of those previously reported for more extensively glycosylated compounds Lac(5) and Lac(8). They all strongly bind to the luciferase-encoding plasmid DNA pCMVluc (7040 base-pairs) with a saturation stoichiometry of Lac(n)/P approximately =0.5 (n=0, 1, or 3) or 0.7 (n=5 or 8), where P stands for a phosphate moiety of the plasmid DNA. The resulting carrier-DNA conjugates are positively charged and monomeric (monomolecular with respect to DNA) as such when n=0 or 1, neutral and monomeric when n=3, or neutral and aggregated when n=5 or 8. Transfection of HeLa (uterine) and HepG2 (hepatic) cell lines shows a general trend of decreasing luciferase expression efficiencies (E) in lively cells as well as cytotoxicities with increasing n's. The cell selectivities for HepG2 over HeLa sharply increase with increasing n's; E(HepG2)/E(HeLa)=0.3, 0.6, 7, 14, and 120 for Lac(0), Lac(1), Lac(3), Lac(5), and Lac(8), respectively, as a result of specific receptor pathway involving the asialoglycoprotein receptors on the hepatic (HepG2) cell surfaces and clustering lactose moieties of the carrier-DNA conjugates. The toxicity-corrected, overall efficiency of gene delivery to hepatocytes is optimized at Lac(3), which forms compactly packed (approximately 40 nm), charge-masked (xi approximately = 0 mV), and less toxic virus-like particles capable of receptor-mediated hepatocyte targeting. |
| 巻・号 | 116(2) |
| ページ | 107-14 |
| 公開日 | 2006-11-28 |
| DOI | 10.1016/j.jconrel.2006.07.004 |
| PII | S0168-3659(06)00332-4 |
| PMID | 16905218 |
| MeSH | Asialoglycoprotein Receptor / metabolism* Cell Survival / drug effects DNA / genetics DNA / metabolism* Female Genes, Reporter Genetic Therapy / methods Glycosylation HeLa Cells Hepatocytes / metabolism* Humans Lactose / chemistry* Luciferases Macrocyclic Compounds / chemistry Macrocyclic Compounds / metabolism* Macrocyclic Compounds / toxicity Particle Size Plasmids Polyamines / chemistry Polyamines / metabolism* Polyamines / toxicity Transfection / methods* Uterus / cytology Uterus / metabolism |
| IF | 7.727 |
| 引用数 | 28 |
| 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 | 3 |
| 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 | HeLa(RCB0007) Hep G2(RCB1648) |