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 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 monitoring of MMP2 secretion from MDA-MB-231 cells and MCF-7 cells, as well as imaging of metastatic lymph nodes, would provide a universal platform for protease secretion study and contribute to tumor invasiveness assessment.
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