Theranostics 2017; 7(11):2878-2887. doi:10.7150/thno.19358

Research Paper

Blood Droplet-Based Cancer Diagnosis via Proteolytic Activity Measurement in Cancer Progression

Jin Woo Choi1*, Hyungbeen Lee2*, Gyudo Lee3, Yi Rang Kim4, Myung-Ju Ahn5, Heung Jae Park6, Kilho Eom7✉, Taeyun Kwon8✉

1. Laboratory of Pharmacogenetics, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea;
2. Department of Biomedical Engineering, Yonsei University, Wonju 26493, Republic of Korea;
3. School of Public Health, Harvard University, Boston, MA 02115, USA;
4. Department of Hemato-Oncology, Yuseong Sun Hospital, Daejeon 34078, Republic of Korea;
5. Section of Hematology-Oncology, Samsung Medical Center, and Sungkyunkwan University (SKKU) School of Medicine, Seoul 06351, Republic of Korea;
6. Department of Urology, Kangbuk Samsung Hospital, Sungkyunkwan University (SKKU) School of Medicine, Seoul 03181, Republic of Korea;
7. Biomechanics Laboratory, College of Sport Science, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea;
8. SKKU Advanced Institute of Nano Technology (SAINT), Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea.
* These authors (J.W.C. and H.L.) made equal contribution to this work.

Abstract

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.

Keywords: proteolysis, matrix metalloproteinase, cancer diagnosis, nanomechanical detection.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Choi JW, Lee H, Lee G, Kim YR, Ahn MJ, Park HJ, Eom K, Kwon T. Blood Droplet-Based Cancer Diagnosis via Proteolytic Activity Measurement in Cancer Progression. Theranostics 2017; 7(11):2878-2887. doi:10.7150/thno.19358. Available from http://www.thno.org/v07p2878.htm