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Nanomaterials 2018, 8(2), 119; https://doi.org/10.3390/nano8020119

Visualization of MMP-2 Activity Using Dual-Probe Nanoparticles to Detect Potential Metastatic Cancer Cells

1
International Research Organization for Advanced Science and Technology (IROAST), Kumamoto University, Kumamoto 860-8555, Japan
2
Magnesium Research Center, Kumamoto University, Kumamoto 860-8555, Japan
3
Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju, Gangwon-do 26493, Korea
4
Department of Biomedical Engineering, Yonsei University, Wonju, Gangwon-do 26493, Korea
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 12 January 2018 / Revised: 13 February 2018 / Accepted: 17 February 2018 / Published: 21 February 2018
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Abstract

Matrix metalloproteinases (MMPs) are a family of zinc-dependent enzymes capable of degrading extracellular matrix components. Previous studies have shown that the upregulation of MMP-2 is closely related to metastatic cancers. While Western blotting, zymography, and Enzyme-Linked Immunosorbent Assays (ELISA) can be used to measure the amount of MMP-2 activity, it is not possible to visualize the dynamic MMP-2 activities of cancer cells using these techniques. In this study, MMP-2-activated poly(lactic-co-glycolic acid) with polyethylenimine (MMP-2-PLGA-PEI) nanoparticles were developed to visualize time-dependent MMP-2 activities. The MMP-2-PLGA-PEI nanoparticles contain MMP-2-activated probes that were detectable via fluorescence microscopy only in the presence of MMP-2 activity, while the Rhodamine-based probes in the nanoparticles were used to continuously visualize the location of the nanoparticles. This approach allowed us to visualize MMP-2 activities in cancer cells and their microenvironment. Our results showed that the MMP-2-PLGA-PEI nanoparticles were able to distinguish between MMP-2-positive (HaCat) and MMP-2-negative (MCF-7) cells. While the MMP-2-PLGA-PEI nanoparticles gave fluorescent signals recovered by active recombinant MMP-2, there was no signal recovery in the presence of an MMP-2 inhibitor. In conclusion, MMP-2-PLGA-PEI nanoparticles are an effective tool to visualize dynamic MMP-2 activities of potential metastatic cancer cells. View Full-Text
Keywords: active matrix metalloproteinase-2; PLGA-PEI nanoparticles; imaging sensor; metastasis active matrix metalloproteinase-2; PLGA-PEI nanoparticles; imaging sensor; metastasis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Lee, A.; Kim, S.H.; Lee, H.; Kim, B.; Kim, Y.S.; Key, J. Visualization of MMP-2 Activity Using Dual-Probe Nanoparticles to Detect Potential Metastatic Cancer Cells. Nanomaterials 2018, 8, 119.

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