A Smart, Autocatalytic, DNAzyme Biocircuit for in Vivo, Amplified, MicroRNA Imaging

Abstract

DNAzymes have been recognized as promising transducing agents for visualizing endogenous biomarkers, but their inefficient intracellular delivery and limited amplification capacity (including insufficient cofactor supply) preclude their extensive biological application. Herein, an autocatalytic DNAzyme (ACD) biocircuit is constructed for amplified microRNA imaging in vivo based on a hybridization chain reaction (HCR) and DNAzyme biocatalysis, sustained by a honeycomb MnO2 nanosponge (hMNS). The hMNS not only delivers DNA probes, but also supplies Mn2+ as a DNAzyme cofactor and magnetic resonance imaging (MRI) agent. Through the subsequent cross‐activation of HCR and DNAzyme amplicons, the ACD amplifies the limited signal resulting from miRNA recognition. The hMNS/ACD system was used to image microRNA in vivo, thus demonstrating its great promise in cancer diagnosis.

An Enzyme‐Activatable Engineered DNAzyme Sensor for Cell‐Selective Imaging of Metal Ions

“…For example, irregular concentrations of metal ions are implicated in a variety of cancers [3, 4] . In order to elucidate their role in diverse pathological processes, DNAzyme, a class of functional DNA that possess catalytic activity, [5, 6] have been widely investigated for development of metal‐ion sensors [7–26] . Compared with small molecular probe, DNAzymes obtained by the in vitro selection have the merits of easy synthesis, high programmability and sensitivity for almost any metal ion [7, 9, 10] .…”

DNA Assembly‐Based Stimuli‐Responsive Systems

“…[349] Based on a HCR and DNAzyme biocatalysis, Wang's group constructed an autocatalytic DNAzyme (ACD) biocircuit sustained by a honeycomb MnO 2 nanosponge (hMNS), which allows simultaneous fluorescence and MR imaging. [350] The stimuli-responsive imaging strategy greatly enriches the toolbox of techniques for bioanalysis in living systems, which is important in the diagnosis of human diseases, especially cancers. www.advancedsciencenews.com www.advancedscience.com…”

Nanoparticle‐Based Activatable Probes for Bioimaging

“…constructed a honeycomb MnO 2 nanosponge‐sustained autocatalytic DNAzyme machine for the robust MRI of the tumor and the concomitant in vivo microRNA imaging. [ 22 ] The reduction by GSH can also affect the metal optical properties of element nanomaterials. For example, MnMoOx nanorods typically do not have optical absorbance in the NIR window.…”

“…[21] Compared with the control group, the relaxivity values (r 1 = 5.12 mm −1 s −1 , r 2 = 265.32 mm −1 s −1 ) were more than twofold at 3.0 T. Also, based on the MnO redox response, Wei et al constructed a honeycomb MnO 2 nanosponge-sustained autocatalytic DNAzyme machine for the robust MRI of the tumor and the concomitant in vivo microRNA imaging. [22] The reduction by GSH can also affect the metal optical properties of element nano materials. For example, MnMoOx nanorods typically do not have optical absorbance in the NIR window.…”