Boolean logic used to trigger drug delivery

Scientists have developed lots of techniques for targeted drug delivery—directly to tumors, for example—to optimize therapeutic efficacy while minimizing side effects. But a new system may be the most “logical” such approach yet devised. In the technique, developed by Cole A. DeForest and coworkers at the University of Washington, drugs stored in polymeric hydrogels are released only when Boolean logic-based chemical gates open (Nat. Chem. 2018, DOI: 10.1038/nchem.2917). The gates open when they encounter precise combinations of environmental cues designed to activate them, such as a particular enzyme or reducing agent present selectively in a tumor. The system is modular, so different stimuli-sensitive gates could be installed in the hydrogel to target drugs to different sites in the body. The researchers showed that a hydrogel with a Boolean AND gate delivered the drug doxorubicin to cancer cells in culture only in the presence of both a matrix metalloprotease and a reducing agent. DeForest and coworkers believe that Boolean targeting could be useful in diagnostics and regenerative medicine as well as in drug delivery.