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Updated: Nov 7, 2025
Nanosensors to Detect Protease Activity In Vivo for Noninvasive Diagnostics
Published on: July 16, 2018
In Situ Protease Secretion Visualization and Metastatic Lymph Nodes Imaging via a Cell Membrane-Anchored Upconversion
Yanyun Fang1, Yuetong Li1, Yuyi Li1
1State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
Abstract:
Matrix metalloproteinase (MMP) secretion is highly associated with tumor invasion and metastasis; therefore, monitoring MMP secretion is important for disease progression study and therapy choosing. Though working well for intracellular MMP imaging, the performance of current MMP detection probes is impaired in secretion monitoring due to the diffusion of MMP in an extracellular environment after secretion and low secreted amount. Here, we design a cell membrane-anchored ratiometric upconversion nanoprobe (UCNPs-Cy3/Pep-QSY7/Ab) for in situ MMP secretion visualization. Anti-EGFR is functionalized on the nanoprobe to provide specific recognition to tumor cells and guarantee fast response to MMP2 in the local place of secretion. MMP-responsive cleavage of Pep-QSY7 results in Cy3 luminescence recovery at 580 nm, which is ratioed over an internal standard of UCNP emission at 654 nm for MMP2 detection. The presented cell membrane-anchored ratiometric upconversion nanoprobe demonstrated that satisfactory results for in situ monitoring of MMP2 secretion from MDA-MB-231 cells and MCF-7 cells, as well as in vivo imaging of metastatic lymph nodes, would provide a universal platform for protease secretion study and contribute to tumor invasiveness assessment.
Insights
This study introduces a novel cell membrane-anchored nanoprobe for real-time visualization of matrix metalloproteinase (MMP) secretion. This tool enhances tumor invasion assessment and therapeutic strategy selection.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Matrix metalloproteinase (MMP) secretion is crucial for tumor invasion and metastasis, necessitating effective monitoring for disease progression and treatment selection.
- Current MMP detection probes struggle with extracellular monitoring due to diffusion and low secretion levels, limiting their utility for studying secreted MMPs.
- Developing sensitive and specific tools for in situ MMP secretion visualization is essential for advancing cancer research and diagnostics.
Purpose of the Study:
- To design and develop a cell membrane-anchored ratiometric upconversion nanoprobe for in situ visualization of MMP secretion.
- To enhance the detection of MMP2 in the local tumor microenvironment, improving specificity and response time.
- To provide a versatile platform for monitoring protease secretion and assessing tumor invasiveness.
Main Methods:
- Fabrication of a ratiometric upconversion nanoprobe (UCNPs-Cy3/Pep-QSY7/Ab) anchored to cell membranes.
- Functionalization with anti-EGFR for specific tumor cell recognition and proximity to MMP2 secretion sites.
- Utilizing MMP-responsive cleavage of Pep-QSY7 to trigger Cy3 luminescence recovery, ratioed against UCNP emission for quantitative MMP2 detection.
Main Results:
- The nanoprobe successfully achieved in situ monitoring of MMP2 secretion from MDA-MB-231 and MCF-7 cancer cell lines.
- Demonstrated effective in vivo imaging of metastatic lymph nodes, highlighting the probe's applicability in complex biological systems.
- The ratiometric detection approach provided reliable and sensitive quantification of MMP2 activity.
Conclusions:
- The developed cell membrane-anchored ratiometric upconversion nanoprobe is effective for in situ MMP secretion visualization.
- This platform offers a universal approach for studying protease secretion and contributes to the assessment of tumor invasiveness.
- The findings pave the way for improved diagnostic tools and therapeutic strategies in oncology.
