Spring-Loaded Nanoparticles Sense Proteases

A new polymer nanoparticle acts like a protease mousetrap, glowing bright red only when a specific enzyme is present (J. Am. Chem. Soc., DOI: 10.1021/ja301259v). The developers of the sensor hope the particle will help doctors detect proteases that turn on in the early stages of cancer. Timothy M. Swager and Carlos Cordovilla of Massachusetts Institute of Technology designed their five-block polymer around pentiptycene, which emits red light when ultraviolet light excites it. Swager predicted that if several of the polymers packed tightly in a nanoparticle, the “chains would mingle together,” which would prevent the polymers from emitting light. If given a bit more room, he says, they should start emitting again. The chemists cross-linked the polymer chains with a peptide that had an amino-acid sequence that the protease trypsin would cleave. This cross-linking forced the polymer chains to crowd together closely enough to shut off their fluorescence. When they mixed the dark nanoparticles with trypsin, the enzyme snipped the peptides, allowing the particles to expand. The particles then glowed 15 times as brightly as they did without the protease.