論文 - 詳細
| RRC ID | 43694 |
|---|---|
| 著者 | Ito T, Koyama Y, Otsuka M. |
| タイトル | DNA complex-releasing system by injectable self-setting apatite cement. |
| ジャーナル | J Gene Med |
| Abstract |
BACKGROUND:The therapeutic effect of plasmid DNA complexes is not satisfactory because of the short duration of their gene expression. However, an efficient DNA slow-release system has not been established owing to the low dispersion stability of the DNA/polycation (or cationic lipid) complexes. We have found that hyaluronan (HA) could deposit onto the DNA/polycation complexes, stabilize their dispersion and prepare very small particles. We have also reported that the injectable self-setting apatite cement has high biocompatibility and biodegradability. Thus, durable gene expression systems using injectable apatite cement, including DNA/polycation/HA complexes, were expected. METHODS:Small DNA/polyethyleneimine (PEI)/HA complex particles were prepared by a lyophilizing and rehydration process, and the in vitro release ratio of DNA complex from the apatite cements by MLC-6 cells was examined. Apatite cement slurry with collagen including plasmid DNA (pDNA) complex [encoding granulocyte macrophage-colony stimulating factor (GM-CSF)] was injected close to the tumor subcutaneously inoculated into mice. The therapeutic effect and degradation ratio of the apatite cement were evaluated. RESULTS:Very fine DNA/PEI/HA complex particles kept being dispersed in the apatite cement. The DNA complexes were continuously released from the apatite cement by MLC-6 cells. Single injection of the apatite cement-including pDNA-GM-CSF complex induced complete disappearance of tumor in 60% of mice. Smooth degradation of the apatite cement was observed in the mice in which a high therapeutic effect was seen. CONCLUSIONS:Single injection of the apatite cement-including pDNA-GM-CSF complex showed a high therapeutic effect on solid tumor, and thus appears to be promising as a sustained gene expression device. |
| 巻・号 | 14(4) |
| ページ | 251-61 |
| 公開日 | 2012-4-1 |
| DOI | 10.1002/jgm.2613 |
| PMID | 22367981 |
| MeSH | Animals Apatites / administration & dosage Apatites / chemistry* Bone Cements / chemistry* Cells, Cultured DNA / chemistry* Granulocyte-Macrophage Colony-Stimulating Factor / genetics Injections Mice Polyethyleneimine / chemistry Transfection |
| IF | 3.258 |
| 引用数 | 4 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL BIOTECHNOLOGY & APPLIED MICROBIOLOGY GENETICS & HEREDITY |
| リソース情報 | |
| ヒト・動物細胞 | |