Exploiting Enzyme Alterations in Cancer for Drug Activation, Drug Delivery, and Nanotherapy.

Alterations of enzyme activity or enzyme levels in cancer tissue have been documented over the years. Taking advantage of these observations, various strategies for drug activation and drug delivery have been developed. One example is a mechanism called "prodrugs" that generates active drugs by enzyme cleavage. Another example is enzyme-induced anticancer drug release mechanisms. This system is constructed by incorporating enzyme-sensitive linkages to materials such as hydrogels and nanodelivery vehicles, including liposomes, polymer micelles, and mesoporous silica nanoparticles. Various release mechanisms for anticancer drugs and siRNA have been developed. In addition, enzyme cleavage is utilized in nanodelivery vehicles that contain nanomachines. One example is nanovalve that can be opened by enzyme cleavage. Another example is enzyme-induced release of nanoparticles from multistage vehicles. Finally, colon-specific drug delivery by azoreductase cleavable mechanism is discussed.