Molecular Beacons Resist Degradation

Molecular beacons are biological detection agents that fluoresce in the presence of specific reactions or enzymes. In the beacons, a fluorophore is linked to a fluorescence-quenching group. When a specific reaction or enzyme breaks the link, the beacon fluoresces. But beacons often break up prematurely, causing false-positive indications. Honggang Cui and coworkers at Johns Hopkins University have devised a potential fix. They add a peptide that makes beacons amphiphilic, inducing them to assemble into spherical micelles with the links inside, where they can’t be broken unintentionally (ACS Nano 2013, DOI: 10.1021/nn400218a). In the presence of pH or dilution changes, such as those that occur in tumors or other sites where detection is needed, the micelles break up and the beacons become active. Cui and coworkers demonstrate the technology by using beacons to detect and quantify the lysosomal enzyme cathepsin B, which plays a key role in tumor growth. They now plan to further refine the micelle dissociation process and incorporate nonfluorescent probes that will enable the beacons to work in deep tissue, where fluorescence can’t be detected.