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Open AccessCommunication

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

by Aeju Lee 1,2,†, Sung Hoon Kim 3,†, Hyun Lee 4, Bohee Kim 3, Yoon Suk Kim 3 and Jaehong Key 4,*
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
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Nanomaterials 2018, 8(2), 119; https://doi.org/10.3390/nano8020119
Received: 12 January 2018 / Revised: 13 February 2018 / Accepted: 17 February 2018 / Published: 21 February 2018
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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MDPI and ACS Style

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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