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

Abstract

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 Cu 2+ cofactor of the Cu 2+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 Cu 2+ , 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. Cu 2+ -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.

Recent Advances on DNAzyme‐Based Sensing

“…(D) DNAzyme logic circuits coupling with MOF for intracellular miRNAs imaging. Reproduced with permission [82] . Copyright 2021, American Chemical Society.…”

“…This proposed DNAzyme−AuNPs nanomachine exhibited both enhanced stability and catalytic activity compared to that of commercial transfection reagent and FISH probes. In another example, the Chu group developed DNAzyme logic circuits‐encapsulated Cu/ZIF‐8 nanosystems for microRNA imaging (Figure 6D) [82] . Cu/ZIF‐8 nanoparticles worked not only as the nanocarrier for DNAzyme delivery, but provided Cu 2+ cofactor to accelerate the cleavage of DNAzyme.…”

Spatiotemporally Controlled Ultrasensitive Molecular Imaging Using a DNA Computation-Mediated DNAzyme Platform

“…Ultrasensitive and precise intracellular biomolecule imaging is of great significance for accurate disease diagnosis and prognostic estimation. − As a class of functional single-stranded DNA that possesses enzymatic properties, deoxyribozyme (DNAzyme) based-probes have become promising candidates for molecular imaging and attracted tremendous interest owing to their merits of flexible programmability and facile synthesis. − Compared with traditional imaging probes, DNAzyme probes can be easily designed for different applications by introducing the desired DNAzyme with specifically programmable sequences that can recognize different targets. , Accordingly, considerable endeavors have been devoted to develop DNAzyme probes for imaging analysis of various disease-related species including miRNAs, , metal ions, − pathogens − other clinically relevant biomarkers, − and so forth. Despite these progresses, the following two non-negligible limitations of the reported DNAzyme probes still prevent their widespread bio-imaging application: (1) traditional DNAzyme probes are continuously in a “always-active” state and passive signal responses will be unavoidably generated when they encountered with targets at undesired time point and position, resulting in the false positive signals; (2) detection sensitivity will be unavoidably reduced because of the photo-bleaching and weak fluorescence signals at low concentration of the fluorescent dyes labeled for DNAzyme probes.…”

Fluorescent Detection of Two Pesticides Based on CRISPR-Cas12a and Its Application for the Construction of Four Molecular Logic Gates

“…By simulation of the binary operation of the computer, molecular logic gate can receive biomolecules as inputs to generate different output signals . A binary code was used to define the state of inputs and outputs . The absence and presence of an input was defined as 0 and 1, respectively.…”

“…2 A binary code was used to define the state of inputs and outputs. 3 The absence and presence of an input was defined as 0 and 1, respectively. The output signal higher or lower than a threshold was defined as 1 and 0, respectively.…”