All-In-One Entropy-Driven DNA Nanomachine for Tumor Cell-Selective Fluorescence/SERS Dual-Mode Imaging of MicroRNA

Analytical Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

An entropy-driven catalysis (EDC) strategy is appealing for amplified bioimaging of microRNAs in living cells; yet, complex operation procedures, lacking cell selectivity, and insufficient accuracy hamper its further applications. Here, we introduce an ingenious all-in-one DNA nanomachine (termed as AIO-EDN), which can be triggered by endogenous apurinic/apyrimidinic endonuclease 1 (APE1) to achieve tumor cell-selective dual-mode imaging microRNA. Compared with the traditional EDC strategy, integrated design AIO-EDN achieves autocatalytic signal amplification without extra fuel strands. Moreover, leverages APE1 overexpressed cancer cells activate reaction, which, however, exerts no target sensing activity normal cells. Combining fluorescence- surface-enhanced Raman scattering (FL/SERS) techniques, this exhibits significantly improved selectivity microRNA This study provides a new paradigm develop EDC-based platform shows great potential in-depth diagnosis high precision.

Язык: Английский

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Scaling up of a Self‐Confined Catalytic Hybridization Circuit for Robust microRNA Imaging

Advanced Science, Год журнала: 2024, Номер 11(22)

Опубликована: Апрель 13, 2024

Abstract The precise regulation of cellular behaviors within a confined, crowded intracellular environment is highly amenable in diagnostics and therapeutics. While synthetic circuitry system through concatenated chemical reaction network has rarely been reported to mimic dynamic self‐assembly system. Herein, catalytic self‐defined circuit (CSC) for the hierarchically assembly DNA domino nanostructures engineered. By incorporating pre‐sealed symmetrical fragments into preying hairpin reactants, CSC allows hierarchical via microRNA (miRNA)‐powered self‐sorting hybridization reaction. With minimal strand complexity, this self‐sustainable streamlined component achieved localization‐intensified cascaded signal amplification. Profiting from self‐adaptively reaction, reliable robust method discriminating carcinoma tissues corresponding para‐carcinoma tissues. CSC‐sustained strategy provides comprehensive smart toolbox organizing various nanostructures, which may facilitate more insights clinical diagnosis therapeutic assessment.

Язык: Английский

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

Analytical Chemistry, Год журнала: 2024, Номер 96(23), С. 9666 - 9675

Опубликована: Май 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.

Язык: Английский

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Harnessing a Self‐Regenerated Hybridization Circuit for Differentiating Heart Failure Patients of Varied Severity

Small, Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

Heart failure (HF) is a globally threatening cardiovascular disease associated with poor quality of life and high mortality, therefore, timely diagnosis risk prediction for HF are urgently needed. Herein, compact yet robust self-regenerated hybridization circuit (SHC) aptasensor developed the amplified detection N-terminal pro-brain natriuretic peptide (NT-proBNP), "gold standard biomarker" HF. The aptamer transduction module can specifically recognize NT-proBNP, thus initiating cascade reaction successively triggers that reversely initiate cross-hybridization reaction. Benefiting from aptamer-specific recognition self-replicated signal amplification, SHC demonstrated more impressive diagnostic performance in elderly patients than clinical fluorescence immunochromatography assay (FICA) terms positive predictive value (21 vs 17), specificity (39 32), accuracy (37 36). Furthermore, this approach allows differentiation among varying severities, achieving sufficiently 78.3%, facilitating accurate therapeutic intervention. versatile reliable system offers new to analyzing low-abundance biomarkers rare specimens, which highly important early prognosis assessment.

Язык: Английский

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

Analytical Chemistry, Год журнала: 2024, Номер 96(31), С. 12854 - 12861

Опубликована: Июль 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

Язык: Английский

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On‐Site Multiply Stimulated Self‐Confinement of an Integrated DNA Cascade Circuit for Highly Reliable Intracellular Imaging of miRNA and In Situ Interrogation of the Relevant Regulatory Pathway

Small, Год журнала: 2024, Номер unknown

Опубликована: Сен. 16, 2024

Abstract Artificial DNA circuits represent a versatile yet promising toolbox for in situ monitoring and concomitant regulation of diverse biological events within live cells. Nonetheless, their performance is significantly impeded by the diffusion‐dominated slow reaction kinetics uncontrollable off‐target activation. Herein, self‐localized cascade (SLC) circuit reported robust efficient microRNA (miRNA) analysis living The SLC consists cell‐specific localization module analyte‐specific signal amplification module. By integrating probes these two modules, complexity system reduced to realize responsive co‐localization circuitry simultaneous amplification. Taking advantage specifically activated, self‐localized, design, successfully achieves miRNA‐21 (miR‐21) imaging accurate cells differentiation. Moreover, reverse mechanism explored between messenger RNA (mRNA) miRNA through engineered further elucidates underlying signaling pathways them. Therefore, provides powerful tool sensitive detection intracellular biomolecules study corresponding cell regulatory mechanisms.

Язык: Английский

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Bioinspired Nucleic Acid-Based Bandpass Filters and Their Concentration-Adaptive Functions

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Апрель 3, 2025

Natural signaling networks can act as bandpass filters to interpret external stimuli within defined concentration ranges for differential cellular activities. Replicating such a filtering mechanism by synthetic poses significant challenge. Herein, we introduce modular design of nucleic acid-based multilayer threshold-gated incoherent feedforward multiband produce mutually exclusive responses input ranges. In these networks, acids demonstrate triple functionality acting entities discern levels, serving network nodes assemble loops nonlinear signal processing, and functioning transduction units coupling downstream functional modules. These enable the fine-tuning performance in terms band position, bandwidth, cascades, responses. A mathematical simulation model allows us predict behaviors under various conditions. Also, are integrated with upstream conversion modules process information on molecules beyond acids, adenosine its derivatives. Furthermore, connections allow system regulate processes manner, realizing concentration-adaptive DNAzyme biocatalysis, tristate logic operations, RNA transcription, DNA condensate formation. findings underscore potential enzyme-free reaction complex processing lay solid foundation developing chemical material systems highly adaptive autonomous behaviors.

Язык: Английский

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

Small, Год журнала: 2025, Номер unknown

Опубликована: Апрель 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

Язык: Английский

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A Novel Fluorescent Sensing Platform for miRNA-210 Detection Based on Signal Amplification via SDA and Self-Assembly Cas12a System via RCT

Talanta, Год журнала: 2025, Номер 295, С. 128382 - 128382

Опубликована: Май 24, 2025

Язык: Английский

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

ChemBioChem, Год журнала: 2024, Номер 25(15)

Опубликована: Май 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.

Язык: Английский

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