Metal-Organic Framework Nanoparticles Power DNAzyme Logic Circuits for Aberrant MicroRNA Imaging

At the molecular level, a large number of studies exist on the use of dynamic DNA molecular circuits for disease diagnosis and biomedicine. However, how to design programmable molecular circuit devices to autonomously and accurately diagnose multiple low-abundance biomolecules in complex cellular environments remains a challenge. Here, we constructed DNAzyme logic circuits for the analysis and imaging of multiple microRNAs in living cells using Cu/ZIF-8 NPs as a nanocarrier of the logic gate modules and the Cu²⁺ cofactor of the Cu²⁺-dependent DNAzyme. The logic gate modules of the logic operation system were adsorbed on the surface of Cu/ZIF-8 NPs via electrostatic interaction. After internalization, pH-responsive Cu/ZIF-8 NPs could efficiently release the logic gate modules and Cu²⁺, which allowed us to realize multiple logic computations initiated by endogenous miRNA, including one YES logic gate and two binary logic gates (OR and AND) in different living cells. Cu²⁺-DNAzyme logic circuits could quickly respond to multiple endogenous miRNAs in the complex cell environment, which also provided a new research method for the application of DNA biocomputing circuits in living cells.