Spatiotemporally Programmed Disassembly of Multifunctional Integrated DNAzyme Nanoplatfrom for Amplified Intracellular MicroRNA Imaging

Abstract The sensing performance of DNAzymes in live cells is tremendously hampered by the inefficient and inhomogeneous delivery of DNAzyme probes and their incontrollable off‐site activation, originating from their susceptibility to nuclease digestion. This requires the development of a more compact and robust DNAzyme‐delivering system with site‐specific DNAzyme activation property. Herein, a highly compact and robust Zn@DDz nanoplatform is constructed by integrating the unimolecular microRNA‐responsive DNA‐cleaving DNAzyme (DDz) probe with the requisite DNAzyme Zn 2+ ‐ion cofactors, and the amplified intracellular imaging of microRNA via the spatiotemporally programmed disassembly of Zn@DDz nanoparticles is achieved. The multifunctional Zn@DDz nanoplatform is simply composed of a structurally blocked self‐hydrolysis DDz probe and the inorganic Zn 2+ ‐ion bridge, with high loading capacity, and can effectively deliver the initially catalytic inert DDz probe and Zn 2+ into living cells with enhanced stabilities. Upon their entry into the acidic microenvironment of living cells, the self‐sufficient Zn@DDz nanoparticle is disassembled to release DDz probe and simultaneously supply Zn 2+ ‐ion cofactors. Then, endogenous microRNA‐21 catalyzes the reconfiguration and activation of DDz for generating the amplified readout signal with multiply guaranteed imaging performance. Thus, this work paves an effective way for promoting DNAzyme‐based biosensing systems in living cells, and shows great promise in clinical diagnosis.