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In vivo imaging of membrane type-1 matrix metalloproteinase with a novel activatable near-infrared fluorescence probe.

Shimizu Y, Temma T, Hara I, Makino A, Kondo N, Ozeki E, Ono M, Saji H - Cancer Sci. (2014)

Bottom Line: In aqueous buffer, MT1-hIC7L fluorescence was suppressed to background levels and increased approximately 35.5-fold in the presence of detergent.In MT1-MMP negative MCF-7 breast adenocarcinoma cells, both MT1-hIC7L and hIC7L showed no obvious fluorescence.In addition, the fluorescence intensity of C6 cells treated with MT1-hIC7L was suppressed by pre-treatment with an MT1-MMP endocytosis inhibitor (P < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan; Central Institute of Isotope Science, Hokkaido University, Sapporo, Japan.

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Schematic illustration of the design and strategy of MT1-hIC7L. Quenched MT1-hIC7L first attaches to membrane type-1 matrix metalloproteinase (MT1-MMP) expressed on tumor cells, and is then delivered to the cell interior via MT1-MMP internalization whereupon fluorescence signals are emitted following probe degradation.
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fig01: Schematic illustration of the design and strategy of MT1-hIC7L. Quenched MT1-hIC7L first attaches to membrane type-1 matrix metalloproteinase (MT1-MMP) expressed on tumor cells, and is then delivered to the cell interior via MT1-MMP internalization whereupon fluorescence signals are emitted following probe degradation.

Mentions: In this study, we first prepared MT1-hIC7L composed of hIC7L and an anti-MT1-MMP monoclonal antibody. We expected that the quenched MT1-hIC7L would first recognize MT1-MMP expressed on the surface of target tumor cells, and then be delivered into the cell following internalization of MT1-MMP, whereupon probe denaturation or metabolism would result in dequenching of the encapsulated dye and subsequent dye fluorescence (Fig. 1). Therefore, we evaluated the effectiveness of the activatable system in MT1-MMP-expressing tumors and the potential of MT1-hIC7L as a specific imaging probe for MT1-MMP-expressing tumors using in vitro cellular uptake assays and in vivo imaging studies.


In vivo imaging of membrane type-1 matrix metalloproteinase with a novel activatable near-infrared fluorescence probe.

Shimizu Y, Temma T, Hara I, Makino A, Kondo N, Ozeki E, Ono M, Saji H - Cancer Sci. (2014)

Schematic illustration of the design and strategy of MT1-hIC7L. Quenched MT1-hIC7L first attaches to membrane type-1 matrix metalloproteinase (MT1-MMP) expressed on tumor cells, and is then delivered to the cell interior via MT1-MMP internalization whereupon fluorescence signals are emitted following probe degradation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317866&req=5

fig01: Schematic illustration of the design and strategy of MT1-hIC7L. Quenched MT1-hIC7L first attaches to membrane type-1 matrix metalloproteinase (MT1-MMP) expressed on tumor cells, and is then delivered to the cell interior via MT1-MMP internalization whereupon fluorescence signals are emitted following probe degradation.
Mentions: In this study, we first prepared MT1-hIC7L composed of hIC7L and an anti-MT1-MMP monoclonal antibody. We expected that the quenched MT1-hIC7L would first recognize MT1-MMP expressed on the surface of target tumor cells, and then be delivered into the cell following internalization of MT1-MMP, whereupon probe denaturation or metabolism would result in dequenching of the encapsulated dye and subsequent dye fluorescence (Fig. 1). Therefore, we evaluated the effectiveness of the activatable system in MT1-MMP-expressing tumors and the potential of MT1-hIC7L as a specific imaging probe for MT1-MMP-expressing tumors using in vitro cellular uptake assays and in vivo imaging studies.

Bottom Line: In aqueous buffer, MT1-hIC7L fluorescence was suppressed to background levels and increased approximately 35.5-fold in the presence of detergent.In MT1-MMP negative MCF-7 breast adenocarcinoma cells, both MT1-hIC7L and hIC7L showed no obvious fluorescence.In addition, the fluorescence intensity of C6 cells treated with MT1-hIC7L was suppressed by pre-treatment with an MT1-MMP endocytosis inhibitor (P < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan; Central Institute of Isotope Science, Hokkaido University, Sapporo, Japan.

Show MeSH
Related in: MedlinePlus