Probing the Matrix
Since the matrix metalloproteinases (MMPs) are involved in the degradation and turnover of many components of the extracellular matrix (ECM) of a cell,1 it makes sense that they would be a target for cancer treatment and tumor imaging. There are 23 different MMPs in humans and they are closely related. This close relation creates challenges in finding specific substrates, since a single substrate may be cleaved by several MMP enzymes, due to overlapping specificities. As reported in Biomaterials Science, a team, led by Lu Sun, designed a fluorescent nanoprobe that is highly selective for MMP-2. They selected MMP-2 since it was overexpressed in the tumor cells of interest, as well as for its ability to access the cleavage site. They designed their probe by combining a fluorescent fusion protein, a cell-penetrating peptide (CPP), the MMP-2 cleavage site, and immobilized it by chelation to a nickel ferrite nanoparticle surface. In order to measure activation of the probe by tumor-secreted MMP-2, a cell assay was performed with a FRET peptide, MOCAc-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 (MOC-3163-v). The assay confirmed that their selective nanoprobe was only activated by MMP-2.The strategy could pave the way for new, selective MMP probes for use in intracellular tumor imaging.2
- D. Rodríguez et al., Biochimica et Biophysica Acta, 1803 (1), 39 (2010).
- L. Sun et al., Biomater. Sci., (2018). Advance Article