Near-infrared triple-helical peptide with quenched fluorophores for optical imaging of MMP-2 and MMP-9 proteolytic activity in vivo.
Near-infrared triple-helical peptide with quenched fluorophores for optical imaging of MMP-2 and MMP-9 proteolytic activity in vivo.
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DOI：
10.1016/j.bmcl.2014.06.072
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发表时间：
2014-08-15
影响因子：
2.7
通讯作者：
Edwards WB
中科院分区：
文献类型：
--
作者：
Zhang X;Bresee J;Fields GB;Edwards WB
明胶酶家族中的明胶酶成员一直与肿瘤的侵袭性有关，这使得它们成为分子成像的一个有吸引力的目标。我们报道了新的可激活的蛋白水解性光学显像剂，它由三螺旋多肽(THP)结合物组成，对明胶酶具有高度的特异性，含有猝灭的cypate染料。在猝灭效率高达51%的情况下，用荧光分子断层扫描技术监测了明胶酶(分别为6.4×103M−1 S−1至9.1×103M−1 S−1对MMP2和MMP9的kcat/kM值)对人纤维肉瘤移植瘤小鼠3-THP水解酶的荧光信号。肿瘤内有显著的荧光增强，这种增强可被PAN-基质金属蛋白酶抑制剂Ilomastat治疗而减弱。这些数据，结合在体外观察到的明胶酶底物的特异性，表明在肿瘤部位观察到的荧光是由于明胶酶介导的cypate3-THP的水解。
The gelatinase members of the MMP family have consistently been associated with tumor invasiveness, which make them an attractive target for molecular imaging. We report new activatable proteolytic optical imaging agents that consist of triple-helical peptide (THP) conjugates, with high specificity to the gelatinases, bearing quenched cypate dyes. With quenching efficiencies up to 51%, the amplified fluorescence signal upon cypate3-THP hydrolysis by the gelatinases (kcat/KM values of 6.4 × 103 M−1 s−1 to 9.1 × 103 M−1 s−1 for MMP-2 and MMP-9, respectively) in mice bearing human fibrosarcoma xenografted tumors was monitored with fluorescence molecular tomography. There was significant fluorescence enhancement within the tumor and this enhancement was reduced by treatment with pan-MMP inhibitor, Ilomastat. These data, combined with the gelatinase substrate specificity observed in vitro, indicated the observed fluorescence at the site of the tumor was due to gelatinase mediated hydrolysis of cypate3-THP.