| 論文種別 | 原著(症例報告除く) |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | In vivo imaging of membrane type-1 matrix metalloproteinase with a novel activatable near-infrared fluorescence probe |
| 掲載誌名 | 正式名：CANCER SCIENCE ISSNコード：1347-9032/1349-7006 |
| 出版社 | WILEY-BLACKWELL |
| 巻・号・頁 | 105(8),pp.1056-1062 |
| 著者・共著者 | Yoichi Shimizu,Takashi Temma,Isao Hara,Akira Makino,Naoya Kondo,Ei-ichi Ozeki,Masahiro Ono,Hideo Saji |
| 発行年月 | 2014/08 |
| 概要 | Membrane type-1 matrix metalloproteinase (MT1-MMP) is a protease activating MMP-2 that mediates cleavage of extracellular matrix components and plays pivotal roles in tumor migration, invasion and metastasis. Because in vivo noninvasive imaging of MT1-MMP would be useful for tumor diagnosis, we developed a novel near-infrared (NIR) fluorescence probe that can be activated following interaction with MT1-MMP in vivo. MT1-hIC7L is an activatable fluorescence probe comprised of anti-MT1-MMP monoclonal antibodies conjugated to self-assembling polymer micelles that encapsulate NIR dyes (IC7-1, em: 858nm) at concentrations sufficient to cause fluorescence self-quenching. In aqueous buffer, MT1-hIC7L fluorescence was suppressed to background levels and increased approximately 35.5-fold in the presence of detergent. Cellular uptake experiments revealed that in MT1-MMP positive C6 glioma cells, MT1-hIC7L showed significantly higher fluorescence that increased with time as compared to hIC7L, a negative control probe lacking the anti-MT1-MMP monoclonal antibody. In MT1-MMP negative MCF-7 breast adenocarcinoma cells, both MT1-hIC7L and hIC7L showed no obvious fluorescence. In addition, the fluorescence intensity of C6 cells treated with MT1-hIC7L was suppressed by pre-treatment with an MT1-MMP endocytosis inhibitor (P<0.05). In vivo optical imaging using probes intravenously administered to tumor-bearing mice showed that MT1-hIC7L specifically visualized C6 tumors (tumor-to-background ratios: 3.8 +/- 0.3 [MT1-hIC7L] vs 3.1 +/- 0.2 [hIC7L] 48h after administration, P<0.05), while the probes showed similarly low fluorescence in MCF-7 tumors. Together, these results show that MT1-hIC7L would be a potential activatable NIR probe for specifically detecting MT1-MMP-expressing tumors. |
| DOI | 10.1111/cas.12457 |
| PMID | 24863849 |