Multiply Guaranteed Catalytic DNA Circuit for Cancer-Cell-Selective Imaging of miRNA and Robust Evaluation of Drug Resistance

Analytical Chemistry, Journal Year: 2024, Volume and Issue: 96(14), P. 5560 - 5569

Published: March 26, 2024

Catalytic DNA circuits are desirable for sensitive bioimaging in living cells; yet, it remains a challenge to monitor these intricate signal communications because of the uncontrolled circuitry leakage and insufficient cell selectivity. Herein, simple yet powerful DNA-repairing enzyme (APE1) activation strategy is introduced achieve site-specific exposure catalytic circuit realizing selectively amplified imaging intracellular microRNA robust evaluation APE1-involved drug resistance. Specifically, reactants firmly blocked by recognition/cleavage site prevent undesirable off-site leakage. The caged has no target-sensing activity until its components activated via enzyme-mediated structural reconstitution finally transduces fluorescence within miRNA stimulation. designed demonstrates an enhanced signal-to-background ratio assay as compared with conventional enables cancer-cell-selective miRNA. In addition, shows sensing performance visualizing APE1-mediated chemoresistance cells, which anticipated in-depth clinical diagnosis chemotherapy research.

Language: Английский

---

An Intelligent Redox‐Responsive DNA Circuit for Robust On‐Site Profiling of Glutathione‐MicroRNA Signaling Pathway

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(26)

Published: Feb. 22, 2024

Abstract Synthetic biochemical circuits (e.g., DNA circuits) remain at the forefront of intracellular biosensing tasks yet are hindered by undesired off‐site activation and accompanying signal leakage. Herein, study attempts to overcome this limitation developing a simple‐yet‐powerful endogenous glutathione (GSH)‐regulating tactic that permits robust distinguishable on‐site microRNA (miRNA) imaging under disturbed redox homeostasis. Specifically, hierarchically activated catalytic (HAD) circuit is fabricated grafting disulfide linkage within entropy‐driven circuitry (EDC) reactants. It exemplified HAD system promises spatiotemporally selective microRNA‐21 (miR‐21) in living cells differentiation tumor from normal cells. The correlationship between GSH miRNA extensively explored live cells, can substantially expand toolbox for profiling processes.

Language: Английский

---

A Methylation-Gated DNAzyme Circuit for Spatially Controlled Imaging of MicroRNA in Cells and Animals

Analytical Chemistry, Journal Year: 2024, Volume and Issue: 96(23), P. 9666 - 9675

Published: May 30, 2024

Epigenetic modification plays an indispensable role in regulating routine molecular signaling pathways, yet it is rarely used to modulate self-assembly networks. Herein, we constructed a bioorthogonal demethylase-stimulated DNA circuitry (DSC) system for high-fidelity imaging of microRNA (miRNA) live cells and mice by eliminating undesired off-site signal leakage. The simple robust DSC composed primary cell-specific regulation (CR) module ultimate signal-transducing amplifier (SA) module. After the modularly designed was delivered into target cells, DNAzyme CR site-specifically activated endogenous demethylase produce fuel strands subsequent miRNA-targeting SA Through on-site multiply guaranteed recognitions, lucid efficient realized reliably amplified vivo miRNA sensing enabled in-depth exploration demethylase-involved pathway with cells. Our bioorthogonally on-site-activated represents universal versatile biomolecular platform via various regulations shows more prospects different personalized theragnostics.

Language: Английский

---

External stimulation-controlled dynamic DNA devices for biosensing and biomedical applications

Science China Chemistry, Journal Year: 2023, Volume and Issue: 66(11), P. 3105 - 3115

Published: Oct. 7, 2023

Language: Английский

---

Interplay of graphene–DNA interactions: Unveiling sensing potential of graphene materials

Applied Physics Reviews, Journal Year: 2024, Volume and Issue: 11(1)

Published: Jan. 26, 2024

Graphene-based materials and DNA probes/nanostructures have emerged as building blocks for constructing powerful biosensors. possess exceptional properties, including two-dimensional atomically flat basal planes biomolecule binding. probes serve excellent selective probes, exhibiting specific recognition capabilities toward diverse target analytes. Meanwhile, nanostructures function placement scaffolds, enabling the precise organization of molecular species at nanoscale positioning complex biomolecular assays. The interplay graphene-based has fostered creation intricate hybrid with user-defined architectures. This advancement resulted in significant progress developing novel biosensors detecting DNA, RNA, small molecules, proteins, well sequencing. Consequently, a profound understanding interactions between is key to these biological devices. In this review, we systematically discussed current comprehension interaction materials, elucidated latest advancements probe–graphene-based Additionally, concisely summarized recent research endeavors involving deposition on explored imminent biosensing applications by seamlessly integrating materials. Finally, delineated primary challenges provided prospective insights into rapidly field. We envision that review will aid researchers gaining deeper insight mechanisms DNA–graphene-based biosensors, designing desired applications.

Language: Английский

---

Efficient Intracellular MicroRNA Imaging Based on the Localized and Self-Sustainable Catalytic DNA Assembly Circuit

Analytical Chemistry, Journal Year: 2023, Volume and Issue: 95(27), P. 10398 - 10404

Published: June 29, 2023

Building dynamic biological networks, especially DNA circuits, has provided a powerful prospect for exploring the intrinsic regulation processes of live cells. Nevertheless, efficient intracellular microRNA analysis, available multi-component circuits are constrained by their limited operating speed and efficiency due to free diffusion reactants. Herein, we developed an accelerated Y-shaped catalytic (YDC) circuit high-efficiency imaging microRNA. By grafting hairpin assembly (CHA) reactants into integrated scaffold, CHA probes were concentrated in compact space, thus achieving high signal amplification. Profiting from spatially confined reaction self-sustainably assembled products, YDC system facilitated reliable situ Compared with homogeneously dispersed reactants, could efficiently promote kinetics as well uniform delivery probes, providing robust analytical tool disease diagnosis monitoring.

Language: Английский

---

Endogenous Glutathione-Activated Nucleic Acid Molecular Circuitry for Cell-Specific MicroRNA Imaging

Analytical Chemistry, Journal Year: 2024, Volume and Issue: 96(31), P. 12854 - 12861

Published: July 23, 2024

Sensitive and reliable microRNA imaging in living cells has significant implications for clinical diagnosis monitoring. Catalytic DNA circuits have emerged as potent tools tracking these intracellular biomarkers probing the corresponding biochemical processes. However, their utility is hindered by low resistance to external interference, leading undesired off-site activation consequent signal leakage. Therefore, achieving endogenous control of circuit's preferable target analysis cells. In this study, we attempted address challenge engineering a simple yet effective glutathione (GSH)-regulated hybridization chain reaction (HCR) circuit acquiring high-contrast miRNA imaging. Initially, HCR hairpin reactants were blocked engineered disulfide-integrated duplex, thus effectively passivating sensing function. And precaged was liberated cell-specific GSH molecule, initiating system selectively amplified detection microRNA-21 (miR-21). This approach prevented unwanted leakage before exposure into cells, ensuring robust miR-21 with high accuracy reliability specific tumor Moreover, endogenously responsive established link between small regulatory factors miRNA, thereby enhancing gain. summary, activatable represents versatile toolbox bioanalysis exploration potential signaling pathways

Language: Английский

---

Radiolytic reduction and controlling hybridization of oligodeoxynucleotides bearing phenylazothiazole groups by hypoxic X-irradiation

Chemistry Letters, Journal Year: 2025, Volume and Issue: 54(1)

Published: Jan. 1, 2025

Abstract We have attempted to construct a molecular system that regulates duplex formation by using X-irradiation. As system, we designed oligodeoxynucleotides (ODNs) bearing phenylazothiazole (PAT) groups act as radiation-responsive unit. The existence of PAT in the strand stabilized intercalation, while it was decomposed corresponding hydrazine derivative upon hypoxic irradiation. resulting derivatives lost stabilizing ability for duplex, leading its destabilization. In this study, synthesized ODNs with units and characterized their reaction properties irradiation regulate formation.

Language: Английский

---

Leveraging Demethylase Activation in DNA Circuits to Overcome Signal Leakage for Reliable MicroRNA Bioimaging

Small, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Abstract DNA circuits show great potential in monitoring intracellular biomarkers based on their high programmability, predictability, and unique signal amplification capabilities, yet face challenges from uncontrollable leakage caused by the complex environment. Herein, a demethylase‐activated DNA‐assembly (DAD) circuit is designed for reliable robust imaging of cellular microRNA, incorporating sequential activation hybridization chain reaction (HCR) amplifier system. The DAD consists DNAzyme module microRNA‐recognizing HCR signal‐amplifying module. m 6 A‐modified sequence module, initially possessing temporally caged substrate‐cleavage activity, integrated into probe effectively blocking its miRNA‐sensing capacity. In presence ALKBH5 demethylase, methyl‐modifying unit removed, thus restoring catalytic substrate‐cleaving activity. This process exposed previously toehold region probe, thereby activating sensing miRNA. By leveraging activation, this can substantially enhance signal‐to‐background ratio, enabling highly sensitive miRNA detection efficient differentiation cancerous normal cells. Furthermore, established relationship between demethylase enzyme miRNA, paving way investigating more complicate biological processes intricate signaling pathways within

Language: Английский

---

Construction of Multiply Guaranteed DNA Sensors for Biological Sensing and Bioimaging Applications

ChemBioChem, Journal Year: 2024, Volume and Issue: 25(15)

Published: May 27, 2024

Abstract Nucleic acids exhibit exceptional functionalities for both molecular recognition and catalysis, along with the capability of predictable assembly through strand displacement reactions. The inherent programmability addressability DNA probes enable their precise, on‐demand accurate execution hybridization, significantly enhancing target detection capabilities. Decades research in nanotechnology have led to advances structural design functional probes, resulting increasingly sensitive robust sensors. Moreover, increasing attention has been devoted accuracy sensitivity DNA‐based biosensors by integrating multiple sensing procedures. In this review, we summarize various strategies aimed at These involve guarantee procedures, utilizing dual signal output mechanisms, implementing sequential regulation methods. Our goal is provide new insights into development more sensors, ultimately facilitating widespread application clinical diagnostics assessment.

Language: Английский

---