Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science & Collaborative Innovation Center of Suzhou Nano Science and Technology , Soochow University , Suzhou 215123 , P. R. China.
Department of Chemistry and Chemical Engineering , Jining University , Qufu 273155 , P. R. China.
J Am Chem Soc. 2019 Feb 20;141(7):3265-3273. doi: 10.1021/jacs.8b13628. Epub 2019 Feb 8.
The abnormal expression of tumor-related proteases plays a critical role in cancer invasion, progression, and metastasis. Therefore, it is considerably meaningful to non-invasively assess the proteases' activity in vivo for both tumor diagnosis and therapeutic evaluation. Herein, we report an activatable probe constructed with a near-infrared dye (Cy5.5) and a quencher (QSY21) covalently linked through a peptide substrate of matrix metalloproteinases-2 (MMP-2) that was chosen as a model for tumor-associated proteases. Upon cleavage with activated MMP-2, this probe emitted an MMP-2-concentration-dependent fluorescence. Quite unexpectedly, owing to the variation in the aggregation state of both the dye and its quencher as a consequence of the cleavage, the responsive probe presented a dramatic MMP-2-concentration-dependent absorption at around 680 nm, while that at around 730 nm was MMP-2 concentration independent. These features allowed detection of MMP-2 activity via both fluorescence and photoacoustic (PA) imaging in vitro, respectively. Moreover, taking the PA signal at 730 nm as an internal reference, the PA signal at 680 nm allowed quantitative detection of MMP-2 expression in breast cancer in vivo. We thus envision that our current approach would offer a useful tool for studying the malignant impacts of versatile tumor-associated proteases in vivo.
肿瘤相关蛋白酶的异常表达在癌症的侵袭、进展和转移中起着关键作用。因此，非侵入性地评估体内蛋白酶的活性对于肿瘤的诊断和治疗评估具有重要意义。在此，我们报告了一种由近红外染料（Cy5.5）和猝灭剂（QSY21）通过基质金属蛋白酶-2（MMP-2）的肽底物共价连接构建的可激活探针，该探针被选为肿瘤相关蛋白酶的模型。在被激活的 MMP-2 切割后，该探针发出 MMP-2 浓度依赖性荧光。出乎意料的是，由于切割导致染料和猝灭剂聚集状态的变化，响应性探针在大约 680nm 处表现出显著的 MMP-2 浓度依赖性吸收，而在大约 730nm 处则与 MMP-2 浓度无关。这些特征允许通过体外荧光和光声（PA）成像分别检测 MMP-2 活性。此外，以 730nm 的 PA 信号作为内参，680nm 的 PA 信号允许定量检测体内乳腺癌中 MMP-2 的表达。因此，我们设想我们的当前方法将为研究体内多种肿瘤相关蛋白酶的恶性影响提供有用的工具。
