Choi Jin Woo, Lee Hyungbeen, Lee Gyudo, Kim Yi Rang, Ahn Myung-Ju, Park Heung Jae, Eom Kilho, Kwon Taeyun
Laboratory of Pharmacogenetics, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea.
Department of Biomedical Engineering, Yonsei University, Wonju 26493, Republic of Korea.
Theranostics. 2017 Jul 8;7(11):2878-2887. doi: 10.7150/thno.19358. eCollection 2017.
Matrix metalloproteinase (MMP) is a key marker and target molecule for cancer diagnosis, as MMP is able to cleave peptide chains resulting in degradation of extracellular matrix (ECM), a necessary step for cancer development. In particular, MMP2 has recently been recognized as an important biomarker for lung cancer. Despite the important role of detecting MMP molecules in cancer diagnosis, it is a daunting task to quantitatively understand a correlation between the status of cancer development and the secretion level of MMP in a blood droplet. Here, we demonstrate a nanoscale cancer diagnosis by nanomechanical quantitation of MMP2 molecules under cancer progression with using a blood droplet of lung cancer patients. Specifically, we measured the frequency dynamics of nanomechanical biosensor functionalized with peptide chains mimicking ECM in response to MMP2 secreted from tumors in lung with different metastasis level. It is shown that the frequency shift of the biosensor, which exhibits the detection sensitivity below 1 nM, enables the quantitation of the secretion level of MMP2 molecules during the progression of cancer cells or tumor growth. More importantly, using a blood droplet of lung cancer patients, nanomechanical biosensor is shown to be capable of depicting the correlation between the secretion level of MMP2 molecules and the level of cancer metastasis, which highlights the cantilever-based MMP2 detection for diagnosis of lung cancer. Our finding will broaden the understanding of cancer development activated by MMP and allow for a fast and point-of-care cancer diagnostics.
基质金属蛋白酶（MMP）是癌症诊断的关键标志物和靶分子，因为MMP能够切割肽链，导致细胞外基质（ECM）降解，这是癌症发展的必要步骤。特别是，MMP2最近被认为是肺癌的重要生物标志物。尽管检测MMP分子在癌症诊断中具有重要作用，但要定量了解癌发展状态与血滴中MMP分泌水平之间的相关性却是一项艰巨的任务。在此，我们通过对肺癌患者血滴中MMP2分子进行纳米力学定量，展示了一种纳米级癌症诊断方法。具体而言，我们测量了用模拟ECM的肽链功能化的纳米力学生物传感器在响应不同转移水平的肺癌肿瘤分泌的MMP2时的频率动态。结果表明，生物传感器的频率偏移（其检测灵敏度低于1 nM）能够在癌细胞进展或肿瘤生长过程中对MMP2分子的分泌水平进行定量。更重要的是，使用肺癌患者的血滴，纳米力学生物传感器能够描绘MMP2分子分泌水平与癌症转移水平之间的相关性，这突出了基于悬臂梁的MMP2检测用于肺癌诊断的作用。我们的发现将拓宽对MMP激活的癌症发展的理解，并实现快速和即时护理癌症诊断。
