Visualization of MMP-2 activity using dual-probe nanoparticles to detect potential metastatic cancer cells

Aeju Lee, Sung Hoon Kim, Hyun Lee, Bohee Kim, Yoon Suk Kim, Jaehong Key

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Article number119
JournalNanomaterials
Volume8
Issue number2
DOIs
Publication statusPublished - 2018 Feb 21

Fingerprint

Matrix Metalloproteinase 2
Visualization
Cells
Nanoparticles
Polyetherimides
Metalloproteases
Enzymes
Polyethyleneimine
Immunosorbents
Rhodamines
Fluorescence microscopy

All Science Journal Classification (ASJC) codes

  • Materials Science(all)
  • Chemical Engineering(all)

Cite this

Lee, Aeju ; Kim, Sung Hoon ; Lee, Hyun ; Kim, Bohee ; Kim, Yoon Suk ; Key, Jaehong. / Visualization of MMP-2 activity using dual-probe nanoparticles to detect potential metastatic cancer cells. In: Nanomaterials. 2018 ; Vol. 8, No. 2.
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Visualization of MMP-2 activity using dual-probe nanoparticles to detect potential metastatic cancer cells. / Lee, Aeju; Kim, Sung Hoon; Lee, Hyun; Kim, Bohee; Kim, Yoon Suk; Key, Jaehong.

In: Nanomaterials, Vol. 8, No. 2, 119, 21.02.2018.

Research output: Contribution to journalArticle

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AU - Key, Jaehong

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AB - 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.

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