Activatable FRET Nanosensor for Visualizing MT1-MMP Activity in Single Cancer Cell

Membrane type 1 metalloproteinase (MT1-MMP) is an important marker for tumor malignancy since it can directly degrade extracellular matrix and promote cancer cell metastasis. Detecting MT1-MMP activity of cancer cells is an important index to monitor tumor malignancy in cancer diagnosis. However, there is lack of a simple method which can visualize MT1-MMP activity of a cancer cell with high resolution. Here, a MT1-MMP activatable quantum-dot (QD) nanosensor was engineered to visualize the MT1-MMP activity at the single cell level. The QD-based Forster resonance energy transfer (FRET) nanosensor was cleaved by pericellular MT1-MMP of cancer cells, which resulted in a marked change of donor (QD)/acceptor (Cy3) emission ratio and activated cell penetration sequences allowing uptake by cancer cells. By quantifying cellular FRET images and intracellular accumulation of nanosensor, newly developed nanosensor can differentiate various levels of MT1-MMP activity in cancer cells. Thus our enzyme activatable peptide/QD-based FRET nanosensor can visualize the enzyme activity of a cancer cell, providing a simple method for monitoring tumor malignancy.