Fabricating MnO2 Nanozymes as Intracellular Catalytic DNA Circuit Generators for Versatile Imaging of Base‐Excision Repair in Living Cells

Abstract Nanomaterial/DNA integrated systems have become an emerging tool for intracellular imaging. However, intracellular catalytic DNA circuit is rarely explored. Commonly used nanosystems neglect intracellular DNA assembly, conformation folding and catalytic efficiency, all demanding appropriate metal ion conditions. Herein, MnO 2 nanosheet/DNAzyme (nanozyme) is fabricated as intracellular catalytic DNA circuit generator for high signal amplification, and its operation is reported for monitoring DNA base‐excision repair (BER) in living cells with improved performance. MnO 2 nanosheet works as not only DNA nanocarrier but also as DNAzyme cofactor supplier. The nanozyme is constructed by adsorbing DNA probes on MnO 2 nanosheets, facilitating cellular uptake of DNA. They are rapidly released in cellular environments by reducing MnO 2 nanosheets to Mn 2+ as DNAzyme cofactor. After repair enzyme activation, nanozymes are properly assembled with active folded conformation and hold sustained catalytic efficiency over many cycles. It offers at least 40‐fold amplified signals for the monitoring of apurinic/apyrimidinic endonuclease‐initiated and DNA glycosylase‐initiated BER pathways. Multiplex imaging can be allowed by integrating several sets of probes with per MnO 2 nanosheet. The MnO 2 nanozyme opens up exciting opportunities for imaging low‐abundance biomarkers and relevant biological pathways in living cells.