Acid-SwitchableDNAzyme Nanodevice for Imaging MultipleMetal Ions in Living Cells

Metal-assisted deoxyribozyme catalysis\n(DNAzyme) has been a general\nplatform for constructing highly sensitive and selective detection\nsensors of metal ions. However, the “always on” mode\nof the traditional DNAzyme sensors greatly limits their application\nin the visual analysis of endogenous metal ions in a complex physiological\nmicroenvironment. To overcome this obstacle, a smart acid-switchable\nDNAzyme nanodevice is designed to control the DNAzyme activity in\nliving cells and achieve simultaneous visualization of metal ions\n(Zn²⁺ and Pb²⁺) in situ. This nanodevice is\nbuilt on DNAzyme precursors (DPs) and acid-switchable DNA (SW-DNA),\nprecisely responding to pH variations in the range of 4.5–7.0,\nand the state of the three-strand hybridization of DPs successfully\nrenders the DNAzymes inactive before being transported into cells.\nOnce the nanodevice is taken up into living cells, the SW-DNA will\nchange the configuration from linear to triplex in the acidic intracellular\ncompartments (lysosomes, pH ∼4.5 to 5.0) and then the strands\nhybridized with the SW-DNA are liberated and subsequently react with\nDPs to form the active DNAzyme, which can further realize multi-imaging\nof intracellular metal ions. Moreover, this strategy has broad prospects\nas a powerful platform for constructing various acid-switchable nanodevices\nfor visual analysis of multiple biomolecules in living cells.