Enzyme-Initiated Assembly of an Extracellular-Like Two-Dimensional Nanonetwork as a Method to Detect Procancerous Activity.

Extracellular matrix (ECM) enzymes such as lysyl oxidase (LOX) provide a new possibility to contain the invasive progress of cancer. Unlike conventional enzymes, the activity of ECM enzymes is not simply the conversion of the substrate to the product; the amount of enzymes such as matrix metalloproteinases in the ECM changes the structural integrity and morphology of the ECM. These are all important aspects that must be monitored in a spatiotemporally coupled fashion to fully understand their procancerous effect. To achieve this goal, a new molecular probe is developed, which, unlike antibodies or aptamers, can interact with the target enzyme in a more interactive way: the probe can withdraw the metal ion cofactor of the enzyme and modulate its catalytic ability. This can lead to self-propagated cross-linking of the probes to form a network not dissimilar to the collagen and elastin network of the ECM, formed through LOX activity. Thus, the biosensing process itself is a biomimetic of what may occur in vivo in the ECM, and three distinct types of signal readouts can be simultaneously recorded on the sensing surface to provide a fuller picture of ECM enzyme activity, not achievable with traditional designs. Using this method, a parallel between the detected signal and the progress of colorectal cancer can be observed. These results may point to prospective application of this method in evaluating ECM-related tumor invasiveness in the future.