A novel strategy to enhance specificity of MT1-MMP-activatable fluorescent probe for tumor imaging
作者单位：Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics （Theranostics）School of PharmacyTianjin Medical University
会议名称：《第十届全国化学生物学学术会议》
会议日期：2017年
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：Project supported by the National Natural Science Foundation of China (21402143 and 81402856) Tianjin Municipal Science and Technology Commission (15JCQNJC13600 and 15JCYBJC28700)
关 键 词：MT1-MMP peptide substrate specificity activatable fluorescent probe
摘 要：The overlapping substrate specificities within the family of MMP（Matrix Metalloproteinase） enzymes which were associated with tumorigenesis, adds the potential for a substrate to be cleaved by multiple enzymes within this family, this leads to a decreasing specificity of MMP substrate-based probes. In this study, we reported a novel strategy to enhance specificity of membrane type-1 matrix metalloproteinase（MT1-MMP）-activatable fluorescent probe for tumor detection, with the combination of advanced MT1-MMP FRET（fluorescence resonance energy transfer） substrate and specific binding peptide. This probe was fabricated with a reported MT1-MMP specific binding peptide and a MMP peptide substrate via PEG linker. The specificity of probe was enhanced by inducing the specific binding peptide, and keeping the ability of amplify output imaging signals in response to MMP activity with the FRET peptide substrate. Results indicated that the specificity of probe was varied with the lengths of PEG linker, and optimally presented at an intermediate length（PEG chain with 12 subunits, PEG12）. To this regard, the presented activatable probe system deems to be an appealing platform to achieve selective tumor imaging.