論文 - 詳細
| RRC ID | 43013 |
|---|---|
| 著者 | Hatakeyama H, Akita H, Ishida E, Hashimoto K, Kobayashi H, Aoki T, Yasuda J, Obata K, Kikuchi H, Ishida T, Kiwada H, Harashima H. |
| タイトル | Tumor targeting of doxorubicin by anti-MT1-MMP antibody-modified PEG liposomes. |
| ジャーナル | Int J Pharm |
| Abstract |
Immunoliposomes are potent carriers for targeting of therapeutic drugs to specific cells. Membrane type-1 matrix metalloproteinase (MT1-MMP), which plays an important role in angiogenesis, is expressed on angiogenic endothelium cells as well as tumor cells. Then, the MT1-MMP might be useful as a target molecule for tumor and neovascularity. In the present study, we addressed a utility of antibodies against the MT1-MMP as a targeting ligand of liposomal anticancer drug. Fab' fragments of antibody against the MT1-MMP were modified at distal end of polyethylene glycol (PEG) of doxorubicin (DXR)-encapsulating liposomes, DXR-sterically stabilized immunoliposomes (DXR-SIL[anti-MT1-MMP(Fab')]). Modification with the antibody significantly enhanced cellular uptake of DXR-SIL[anti-MT1-MMP(Fab')] into the HT1080 cells, which highly express MT1-MMP, compared with the non-targeted liposomes (DXR-stealthliposomes (DXR-SL)), suggesting that MT1-MMP antibody (Fab') is a potent targeting ligand for the MT1-MMP expressed cells. In vivo systemic administration of DXR-SIL[anti-MT1-MMP(Fab')] into the tumor-bearing mice showed significant suppression of tumor growth compared to DXR-SL. This is presumably due to the active targeting of immunoliposomes for tumor and neovascularity. However, tumor accumulation of DXR-SIL[anti-MT1-MMP(Fab')] and DXR-SL were comparable, suggesting that both liposomal formulations accumulated in tumor via enhanced permeation and retention (EPR) effect, but not via targeting to the MT1-MMP expressed on both the endothelial and tumor cells. It appears that the enhanced antitumor activity of DXR-SIL[anti-MT1-MMP(Fab')] resulted from acceleration of cellular uptake of lioposomes owing to the incorporated antibody after extravasation from capillaries in tumor. |
| 巻・号 | 342(1-2) |
| ページ | 194-200 |
| 公開日 | 2007-9-5 |
| DOI | 10.1016/j.ijpharm.2007.04.037 |
| PII | S0378-5173(07)00361-4 |
| PMID | 17583453 |
| MeSH | Animals Antibiotics, Antineoplastic / administration & dosage Antibiotics, Antineoplastic / therapeutic use* Antibodies, Monoclonal / chemistry Antibodies, Monoclonal / pharmacology Doxorubicin / administration & dosage Doxorubicin / therapeutic use* Drug Compounding Drug Delivery Systems Excipients Immunochemistry Immunoglobulin Fab Fragments / chemistry Liposomes Male Matrix Metalloproteinase 14 / immunology* Mice Mice, Inbred BALB C Neoplasms, Experimental / drug therapy Neoplasms, Experimental / metabolism Polyethylene Glycols / chemistry |
| IF | 4.845 |
| 引用数 | 127 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| 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 | 3.0 |
| リソース情報 | |
| ヒト・動物細胞 | |