Adv. Mater. http://doi.org/wwh (2014)

Credit: © Wiley

Legumain, a protease that has been shown to be over-expressed in tumour-associated macrophages and cancer cells, is believed to promote tumour growth and metastasis. Hence, the activity of legumain in cancer and other inflammation-related diseases could reveal important information about tumourigenesis and aid the diagnosis and prognosis of various diseases. Now, Cheng Luo, Yongzhuo Huang and colleagues have designed a fluorescence-based probe that can be activated by legumain in vitro and in vivo. Molecular dynamics simulations are used to establish appropriate peptide sequences such that cleavage sites are available for legumain-mediated hydrolysis and so that paired dye molecules (a fluorophore–quencher pair) are positioned as close together as possible. In close proximity, the fluorescence of the fluorophore is quenched but cleavage of the peptides by legumain releases the fluorophore and fluorescence is recovered. Fluorescence was observed in legumain-expressing colon cancer cell lines but was absent in control cell lines. Using ex vivo imaging methods, the probe could also distinguish tumours from adjacent healthy tissues and could locate newly developed small tumours.