Self-Assembled Gold Nanoparticle Molecular Probes for Detecting Proteolytic Activity

Target-activatable fluorogenic probes based on gold nanoparticles (AuNPs) functionalized with self-assembled heterogeneous monolayers of dye-labeled peptides and poly(ethylene glycol) have been developed to visualize proteolytic activity in vivo. A one-step synthesis strategy that allows simple generation of surface-defined AuNP probe libraries is presented as a means of tailoring and evaluating probe characteristics for maximal fluorescence enhancement after protease activation. Optimal AuNP probes targeted to trypsin and urokinase-type plasminogen activator required the incorporation of a dark quencher to achieve 5- to 8-fold signal amplification. These probes exhibited extended circulation time in vivo and high image contrast in a mouse tumor model.National Institutes of Health (U.S.) (NIH grant CA119402)National Institutes of Health (U.S.) (grant DE013023)National Institutes of Health (U.S.) (grant DE016516)National Science Foundation (U.S.). Materials Research Science and Engineering Centers (Program) (award number DMR-08-19762