Acid-Switchable DNAzyme Nanodevice for Imaging Multiple Metal Ions in Living Cells

Metal-assisted deoxyribozyme catalysis (DNAzyme) has been a general platform for constructing highly sensitive and selective detection sensors of metal ions. However, the "always on" mode of the traditional DNAzyme sensors greatly limits their application in the visual analysis of endogenous metal ions in a complex physiological microenvironment. To overcome this obstacle, a smart acid-switchable DNAzyme nanodevice is designed to control the DNAzyme activity in living cells and achieve simultaneous visualization of metal ions (Zn²⁺ and Pb²⁺) in situ. This nanodevice is built on DNAzyme precursors (DPs) and acid-switchable DNA (SW-DNA), precisely responding to pH variations in the range of 4.5-7.0, and the state of the three-strand hybridization of DPs successfully renders the DNAzymes inactive before being transported into cells. Once the nanodevice is taken up into living cells, the SW-DNA will change the configuration from linear to triplex in the acidic intracellular compartments (lysosomes, pH ∼4.5 to 5.0) and then the strands hybridized with the SW-DNA are liberated and subsequently react with DPs to form the active DNAzyme, which can further realize multi-imaging of intracellular metal ions. Moreover, this strategy has broad prospects as a powerful platform for constructing various acid-switchable nanodevices for visual analysis of multiple biomolecules in living cells.