Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, United States.
Mol Pharm. 2011 Dec 5;8(6):2331-8. doi: 10.1021/mp2002297. Epub 2011 Nov 1.
Herein we demonstrate for the first time that a fluorogenic probe can be used as an in vivo imaging agent for visualizing activities of membrane-tethered, membrane-type matrix metalloproteinases (MT-MMPs). An MT-MMP fluorogenic probe that consisted of an MT1-MMP (MMP-14) substrate and near-infrared (NIR) dye-quencher pair exhibited rapid, efficient boosts in fluorescence upon cleavage by MT1-MMP in tumor-bearing mice. In particular, unlike similar fluorogenic probes designed to target extracellular, soluble-type MMPs (EC-MMPs)--which can be cleared from the bloodstream after activation--the fluorescence signals activated by MT1-MMP enable clear visualization of MT1-MMP-positive tumors in animal models for up to 24 h. The results indicate that a simple form of a fluorogenic probe that is less effective in EC-MMP imaging is an effective probe for imaging MT-MMP activities in vivo. These findings can be widely applied to designing probes and to applications targeting various membrane-anchored proteases in vivo.
在此，我们首次证明了荧光探针可用作体内成像剂，用于可视化膜结合型、膜型基质金属蛋白酶（MT-MMPs）的活性。该 MT-MMP 荧光探针由 MT1-MMP（MMP-14）底物和近红外（NIR）染料猝灭剂对组成，在荷瘤小鼠中，当被 MT1-MMP 切割时，其荧光会迅速、有效地增强。特别是，与旨在靶向细胞外可溶性型 MMPs（EC-MMPs）的类似荧光探针不同——在激活后可从血液中清除——由 MT1-MMP 激活的荧光信号可使 MT1-MMP 阳性肿瘤在动物模型中长达 24 小时的清晰可视化。结果表明，一种在 EC-MMP 成像中效果较差的简单形式的荧光探针，是一种在体内成像 MT-MMP 活性的有效探针。这些发现可广泛应用于设计探针和针对体内各种膜锚定蛋白酶的应用。
