An Enzyme‐Activatable Engineered DNAzyme Sensor for Cell‐Selective Imaging of Metal Ions

There is intense interest in imaging intracellular metal ions because of their vital roles in many cellular processes. The challenge has been to develop chemical approaches that can detect metal ions in a cell-type-specific manner. Herein we report the design of an enzyme-activatable DNAzyme sensor technology that can distinguish metal-ion signals in tumor cells from those in normal cells both in vitro and in vivo. Specifically, the sensing activity of a traditional DNAzyme sensor was inhibited by engineering with a blocking sequence containing an abasic site that can be cleaved by cancer-specific enzymes and thus enables the selective recovery of metal-ion sensing capability in cancer cells. We demonstrated that the DNAzyme sensor not only enables cancer-cell-selective sensing and imaging of metal ions through an enzymically activated pathway, but also precise control over its metal-ion sensing activity in tumor-bearing mice. We envision the use of this biosensing technology to probe the biological roles of diverse metal ions in specific diseases.