Dark quenched matrix metalloproteinase fluorogenic probe for imaging osteoarthritis development in vivo

Dark quenched matrix metalloproteinase fluorogenic probe for imaging osteoarthritis development in vivo
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DOI:
10.1021/bc800264z
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发表时间:
2008-09-01
影响因子:
4.7
通讯作者:
Choi, Kuiwon
Choi, Kuiwon
中科院分区:
化学2区
文献类型:
--
作者:
Lee, Seulki;Park, Kyeongsoon;Choi, Kuiwon

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骨关节炎(OA)的早期检测是目前风湿病学领域的一个关键挑战。骨关节炎的生化研究表明,基质金属蛋白酶-13(MMP-13)在软骨降解中起着重要作用。在这项研究中,我们描述了潜在的使用暗淬灭荧光MMP-13探针成像MMP-13在体外和大鼠模型。成像技术涉及使用MMP-13肽底物、近红外(NIR)染料和NIR暗淬灭剂。本研究的结果表明,使用暗淬灭荧光探针允许在体外和OA诱导的大鼠模型中目视检测MMP-13。特别是,通过靶向这种OA生物标志物,可以快速有效地监测、成像和分析OA早期和晚期的症状。我们预计,这种简单而高效的荧光探针将有助于OA患者的临床管理,不仅用于早期诊断,而且用于评估个体患者对新药治疗的反应。
The early detection of osteoarthritis (OA) is currently a key challenge in the field of rheumatology. Biochemical studies of OA have indicated that matrix metalloproteinase-13 (MMP-13) plays a central role in cartilage degradation. In this study, we describe the potential use of a dark-quenched fluorogenic MMP-13 probe to image MMP-13 in both in vitro and rat models. The imaging technique involved using a MMP-13 peptide substrate, near-infrared (NIR) dye, and a NIR dark quencher. The results from this study demonstrate that the use of a dark-quenched fluorogenic probe allows for the visual detection of MMP-13 in vitro and in OA-induced rat models. In particular, by targeting this OA biomarker, the symptoms of the early and late stages of OA can be readily monitored, imaged, and analyzed in a rapid and efficient fashion. We anticipate that this simple and highly efficient fluorogenic probe will assist in the clinical management of patients with OA, not only for early diagnosis but also to assess individual patient responses to new drug treatments.