In situ peptide self-assembly on ionic nanochannel for dynamic monitoring of MMPs in extracellular matrix

The extracellular matrix (ECM) of tumor mediates malignant transformation and distant metastasis with extracellular proteinases, especially the matrix metalloproteinases (MMPs). However, there is no assay method to trace the dynamic content of MMPs in ECM. In this work, we have proposed a strategy by assembling peptide scaffold on ionic nanochannels to monitor the target proteinases. The short peptide unit is designed to induce self-assembly with good stability, biocompatibility and programmability, while ion nanochannels can provide electrochemical response upon the MMP activities. Taking MMP-2 as an example, the peptide unit includes two regions, one for self-assembly and one for bio-recognition, so the assembly region (KLVFF) can self-assemble to nanofiber networks. In the meantime, since the reactive region (PLGVR) has MMP-2 recognition site, the peptide assembly on nanochannel can thus be used for the detection of active MMP-2 in tumor microenvironment, with a wide linear detection range (10 fg/mL-10 ng/mL) and 6.6 fg/mL limit of detection. Moreover, the availability of the established ECM mimic is able to distinguish active MMP-2 from latent proMMP-2 in tumor samples. By designing different peptide units for self-assembly on the ionic nanochannel, the assay platform can be promisingly used for other proteinases in ECM, so this work may provide a useful approach to trace the dynamic content of the MMPs in tumor microenvironment (TEM).