A Smart DNAzyme–MnO₂ Nanosystem for Efficient Gene Silencing

Abstract

DNAzymes hold promise for gene-silencing therapy, but the lack of sufficient cofactors in the cell cytoplasm, poor membrane permeability, and poor biostability have limited the use of DNAzymes in therapeutics. We report a DNAzyme-MnO2 nanosystem for gene-silencing therapy. MnO2 nanosheets adsorb chlorin e6-labelled DNAzymes (Ce6), protect them from enzymatic digestion, and efficiently deliver them into cells. The nanosystem can also inhibit (1)O2 generation by Ce6 in the circulatory system. In the presence of intracellular glutathione (GSH), MnO2 is reduced to Mn(2+) ions, which serve as cofactors of 10-23 DNAzyme for gene silencing. The release of Ce6 generates (1)O2 for more efficient photodynamic therapy. The Mn(2+) ions also enhance magnetic resonance contrast, providing GSH-activated magnetic resonance imaging (MRI) of tumor cells. The integration of fluorescence recovery and MRI activation provides fluorescence/MRI bimodality for monitoring the delivery of DNAzymes.

A smart ZnO@polydopamine-nucleic acid nanosystem for ultrasensitive live cell mRNA imaging by the target-triggered intracellular self-assembly of active DNAzyme nanostructures

“…8 The flexibility in regulating DNAzyme structure by encoding specific functional information in its base sequence turns DNAzyme into an ideal candidate for the development of live cell biosensing platforms. In this work, we have developed a novel DNAzyme-based enzyme-free dual amplification strategy for the fluorescence activation imaging of mRNA under in vivo conditions by using a smart hairpin-DNA-based nanosystem, which can facilitate the cellular uptake of molecular hairpins, protect them from nuclease digestion, and deliver them into the cytoplasm for the target-triggered self-assembly of wire-shaped DNA nanostructures consisting of numerous active DNAzyme subunits inside live cells.…”

Comprehensive Screen of Metal Oxide Nanoparticles for DNA Adsorption, Fluorescence Quenching, and Anion Discrimination

“…[1][2][3][4][5][6] While DNA has been interfaced with metal and carbon-based nanomaterials, [6][7][8][9] limited work was carried out on metal oxide nanoparticles (MONPs). [10][11][12][13][14][15][16][17][18][19][20] MONPs represent a very important class of material due to their unique electronic, optical, magnetic and catalytic properties. DNAfunctionalized MONPs might be useful as a sensor platform for anion detection.…”

DNAzyme Hybridization, Cleavage, Degradation, and Sensing in Undiluted Human Blood Serum

“…17 Most analytical applications of DNAzymes have been demonstrated in clean buffer solutions, while applications in biological sample matrices such as serum or cells are less explored. [18][19][20][21][22][23] On a parallel research front, RNA-cleaving DNAzymes are used for intracellular mRNA cleavage in antiviral and anticancer applications. 24 So far, these studies were performed by measuring only the final outcome (e.g., mRNA or protein suppression) without following the reaction steps.…”