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Updated: Jul 7, 2026
Non-invasive In Vivo Fluorescence Optical Imaging of Inflammatory MMP Activity Using an Activatable Fluorescent Imaging Agent
Published on: May 8, 2017
Fluorescence imaging to assess the matrix metalloproteinase activity and its inhibitor in vivo
Zhihong Zhang1, Jie Yang, Jinling Lu
1Huazhong University of Science and Technology, Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Wuhan 430074, China.
Abstract:
Matrix metalloproteinases (MMPs) are a kind of secretory proteinases. Degradation of the extracellular matrix (ECM) by MMPs enhances tumor invasion and metastasis. To monitor MMPs activity and assess the MMP inhibitor effects in vivo, we constructed a plasmid that encoded a secretory fluorescent sensor named DMC (DsRed2-MSS-CFP expressed from pDisplay vector) that DsRed2 and cyan fluorescent protein (CFP) linked by MMP substrate site (MSS). MDA-MB 435s cells highly expressing endogenetic secretory MMP were transfected with the DMC plasmid so that the DMC could be cleaved by endogenetic MMP and the fluorescence ratio of DsRed2 to CFP was decreased. Treating the cells with GM6001, an MMP inhibitor, blocked the cleavage of DMC and caused an increase of the DsRed2/CFP ratio. The same result was achieved by using an in vivo tumor model that stable DMC-expressing MDA-MB 435s cells inoculated onto the chorioallantoic membrane of developing chick embryos to form primary tumors on the membrane. Thus, the fluorescent sensor DMC is able to sensitively monitor MMP activity and assess MMP inhibitors for anticancer research in vivo. This proves a novel method to efficiently screen and assess the anticancer drug MMP inhibitor in living cells and in vivo tumor models.
Insights
Researchers developed a novel fluorescent sensor (DMC) to monitor matrix metalloproteinase (MMP) activity. This tool effectively assesses MMP inhibitors for anticancer drug development in living cells and in vivo tumor models.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Matrix metalloproteinases (MMPs) are key enzymes involved in extracellular matrix degradation.
- MMP activity is crucial for tumor invasion and metastasis.
- Monitoring MMPs and their inhibitors is vital for anticancer research.
Purpose of the Study:
- To develop a novel secretory fluorescent sensor (DMC) for in vivo monitoring of MMP activity.
- To assess the efficacy of MMP inhibitors using the DMC sensor.
- To establish a new method for screening anticancer drugs targeting MMPs.
Main Methods:
- Constructed a plasmid encoding the DMC fluorescent sensor (DsRed2-MSS-CFP).
- Transfected MDA-MB 435s cells with the DMC plasmid.
- Utilized an in vivo chick embryo tumor model to validate the sensor and inhibitor effects.
Main Results:
- The DMC sensor's fluorescence ratio (DsRed2/CFP) decreased upon cleavage by endogenous MMPs.
- Treatment with an MMP inhibitor (GM6001) blocked DMC cleavage, increasing the DsRed2/CFP ratio.
- The DMC sensor successfully monitored MMP activity and inhibitor effects in both cell cultures and an in vivo tumor model.
Conclusions:
- The DMC fluorescent sensor provides a sensitive method for monitoring MMP activity in real-time.
- DMC is effective for assessing MMP inhibitors in anticancer research.
- This technology offers a novel approach for screening anticancer drugs in vitro and in vivo.
