Near-Infrared-Light-Mediated DNA-Logic Nanomachine for Bioorthogonal Cascade Imaging of Endogenous Interconnected MicroRNAs and Metal Ions

Abstract

The interconnection of microRNAs (miRNAs) and metal ions governs multiple biological processes in disease development and progression. However, developing multiplexed tools for dynamic imaging of these regulators remains a significant challenge. Herein, we report a conceptual approach for the design of an optically controlled DNA nanomachine by introducing a ternary DNAzyme-based, UV light-cleavable DNA scaffold and upconversion nanoparticle to the activatable hybrid chain reaction. We demonstrate that this nanomachine is capable of being effectively operated either in the presence of an endogenous miRNA target or the coexistence of intracellular Zn 2+ and external near-infrared light, resulting in enhanced fluorescence resonance energy transfer signals. With this design, the logic-gated imaging of endogenous miR-21 and Zn 2+ is demonstrated in living cells. More importantly, taking advantages of photoacoustic imaging modality, a combinational logic circuit (AND/OR) is constructed for the bioorthogonal cascade imaging of miR-21 and Zn 2+ in vivo, realizing dynamic monitoring of the correlation of miRNA and metal ions levels. Collectively, our results suggest that this conceptual design possesses the ability to expand the DNA nanomachine toolbox for visualizing a broad spectrum of interconnected molecules and thus provides new perspectives to improve the diagnostic and therapeutic outcomes.

Light-Driven and Metal–Organic Framework Synergetic Loaded DNA Tetrahedral Amplifier for Exonuclease III-Powered All-in-One Biosensing and Chemotherapy in Live Biosystems

“…As a result of these lost fluorescence signals, the concentration corresponding to the location where the DNA amplifiers arrive is unlikely to represent reality, and this inaccurate biosensing has limited therapeutic applications. However, there has been significant development in biosensing modes, and the light-driven concept shows promise for resolving this issue. − As a rule, a simple O -nitrobenzyl-composed photocleavage-linker (PC-linker) can be embedded into the analyte identification component. Subsequently, irradiation with 365 nm ultraviolet (UV) light induces the exposure of the target binding domain with control over the spatiotemporal behavior, thus resulting in more precise biosensing information.…”

Photoresponsive CHA-Integrated Self-Propelling 3D DNA Walking Amplifier within the Concentration Localization Effect of DNA Molecular Framework Enables Highly Efficient Fluorescence Bioimaging

“…At the outset, considering the fact that detection targets are generally present in an extensive way within biological media, a notable concern arises that biosensors inevitably experience premature activation before reaching their intended destination. , Along with such a drawback, a substantial portion of biosensing signals can be lost at any time during biodelivery, leading to the obtained fluorescence data misrepresenting the actual target concentration in the end. Encouragingly, the emergence of an advanced photoresponsive manner offers the hope to overcome the “always-on” state. − To be exact, one DNA component is simply functionalized with an O -nitrobenzyl derivative photocleavage-bond (PC-bond), thereby enabling subsequent target recognition only when the biosensing system is exposed to an external 365 nm ultraviolet (UV) light source. Thanks to this advancement, some studies , have exhibited that DNA-based fluorescent biosensors will be endowed with an entirely controllable spatiotemporal bioimaging ability, allowing for more precise detection.…”

“…Encouragingly, the emergence of an advanced photoresponsive manner offers the hope to overcome the “always-on” state. − To be exact, one DNA component is simply functionalized with an O -nitrobenzyl derivative photocleavage-bond (PC-bond), thereby enabling subsequent target recognition only when the biosensing system is exposed to an external 365 nm ultraviolet (UV) light source. Thanks to this advancement, some studies , have exhibited that DNA-based fluorescent biosensors will be endowed with an entirely controllable spatiotemporal bioimaging ability, allowing for more precise detection. To the best of our knowledge, the consolidation of a photoresponsive manner and 3D DNA walking amplifiers is an innovative effort.…”

Photoactivatable Aptamer-CRISPR Nanodevice Enables Precise Profiling of Interferon-Gamma Release in Humanized Mice

“…In addition, the use of full-length antibody results in decreased tumor penetration and may restrict the probe to peripheral localization . Recent years have witnessed the rapid development of aptamer-based activatable probes for sensing and molecular imaging in living cells and animals because of its high specificity and affinity, small molecular size, on-demand target-triggered activation, and biocompatibility. − While there is a broad spectrum of imaging tools for small molecules, metal ions, − protein enzymes, − or miRNAs, − an aptamer-based activatable probe that permits precise profiling of IFN-γ dynamics in vivo has rarely been explored because of the lack of a design methodology.…”