Self-Stacking Autocatalytic Molecular Circuit with Minimal Catalytic DNA Assembly

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(5), P. 2999 - 3007

Published: Jan. 26, 2023

Isothermal autocatalytic DNA circuits have been proven to be versatile and powerful biocomputing platforms by virtue of their self-sustainable self-accelerating reaction profiles, yet they are currently constrained complicated designs, severe signal leakages, unclear mechanisms. Herein, we developed a simpler-yet-efficient assembly circuit (AAC) for highly robust bioimaging in live cells mice. The scalable sustainable AAC system was composed mere catalytic with minimal strand complexity and, upon specific stimulation, could reproduce numerous new triggers expedite the whole reaction. Through in-depth theoretical simulations systematic experimental demonstrations, efficiency these reproduced found play vital role profile thus facilely improved achieve more efficient characteristic amplification. Due its exponentially high amplification components, our self-stacking facilitated detection trace biomolecules low leakage, providing great clinical diagnosis therapeutic assessment potential.

Language: Английский

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A Smart Deoxyribozyme‐Programmable Catalytic DNA Circuit for High‐Contrast MicroRNA Imaging

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(33)

Published: June 28, 2023

Synthetic catalytic DNA circuits have been recognized as a promising signal amplification toolbox for sensitive intracellular imaging, yet their selectivity and efficiency are always constrained by uncontrolled off-site leakage inefficient on-site circuitry activation. Thus, the endogenously controllable exposure/activation of is highly desirable achieving selective imaging live cells. Herein, an activated DNAzyme strategy was facilely integrated with circuit guiding efficient microRNA in vivo. To prevent activation, constitute initially caged without sensing functions, which could be selectively liberated amplifier to guarantee high-contrast target This intelligent modulation can tremendously expand these molecularly engineered biological systems.

Language: Английский

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The compact integration of a cascaded HCR circuit for highly reliable cancer cell discrimination

Chemical Science, Journal Year: 2023, Volume and Issue: 14(8), P. 2159 - 2167

Published: Jan. 1, 2023

A compact and clamped CHA-control-HCR (CCH) circuitry system, specifically for amplified multi-microRNA imaging, is developed to precisely distinguish cancer cells from normal cells.

Language: Английский

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Miniature Hierarchical DNA Hybridization Circuit for Amplified Multiplexed MicroRNA Imaging

Analytical Chemistry, Journal Year: 2023, Volume and Issue: 95(7), P. 3848 - 3855

Published: Feb. 6, 2023

Accurate diagnosis requires the development of multiple-guaranteed DNA circuits. Nevertheless, for reliable multiplexed molecular imaging, existing circuits are limited by poor cell-delivering homogeneity due to their cumbersome and dispersive reactants. Herein, we developed a compact-yet-efficient hierarchical hybridization (HDH) circuit in situ simultaneous analysis multiple miRNAs, which could be further exploited specifically discriminating cancer cells from normal ones. By integrating traditional chain reaction catalytic hairpin assembly reactants into two highly organized hairpins, HDH is fitted with condensed components response domains, thus permitting programmable microRNA-guaranteed sequential activations localized cascaded signal amplification. The synergistic multi-recognition amplification features facilitate magnified detection multiplex endogenous miRNAs living cells. vitro cellular imaging experimental results revealed that displayed sensing performance high selective cell-identification capacity. We anticipate this compact design can provide powerful toolkit accurate diagnostics pathological evolution.

Language: Английский

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A NIR Programmable In Vivo miRNA Magnifier for NIR‐II Imaging of Early Stage Cancer

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(50)

Published: Oct. 31, 2023

Aberrant expressions of biomolecules occur much earlier than tumor visualized size and morphology change, but their common measurement strategies such as biopsy suffer from invasive sampling process. In vivo imaging slight biomolecule expression difference is urgently needed for early cancer detection. Fluorescence rare earth nanoparticles (RENPs) in second near-infrared (NIR-II) region makes them appropriate tool imaging. However, the incapacity to couple with signal amplification strategies, especially programmable limited application lowly expressed biomarkers Here we develop a 980/808 nm NIR programmed microRNAs (miRNAs) magnifier by conjugating activatable DNAzyme walker set RENPs, which achieves more effective NIR-II stage monitoring technique. Dye FD1080 (FD1080) modified substrate DNA quenches downconversion emission RENPs under 808 excitation. The miRNA recognition sealed photo-cleavable strand avoid "false positive" systemic circulation. Upconversion 980 irradiation activates amplifies fluorescence recovery via catalytic reaction achieve This strategy demonstrates good potential field

Language: Английский

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All-in-One Alkaline Phosphatase-Response Aggregation-Induced Emission Probe for Cancer Discriminative Imaging and Combinational Chemodynamic–Photodynamic Therapy

ACS Nano, Journal Year: 2024, Volume and Issue: 18(27), P. 17837 - 17851

Published: June 28, 2024

Currently, specific cancer-responsive fluorogenic probes with activatable imaging and therapeutic functionalities are in great demand the accurate diagnostics efficient therapy of malignancies. Herein, an all-in-one strategy is presented to realize fluorescence (FL) imaging-guided synergetic chemodynamic–photodynamic cancer by using a multifunctional alkaline phosphatase (ALP)-response aggregation-induced emission (AIE) probe, TPE-APP. By responding abnormal expression levels ALP biomarker cells, phosphate groups on AIE probe selectively hydrolyzed, accompanied situ formation strong emissive aggregates for discriminative cell over normal cells highly active quinone methide species robust activities. Consequently, activated can efficiently destroy membranes lead death within 30 min. A superior efficacy ablation demonstrated vitro vivo. The cancer-associated response-derived FL synergistic expected provide promising avenue precise image-guided therapy.

Language: Английский

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

Advanced Science, Journal Year: 2024, Volume and Issue: 11(22)

Published: April 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.

Language: Английский

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Logic Signal Amplification System for Sensitive Electrochemiluminescence Detection and Subtype Identification of Cancer Cells

Analytical Chemistry, Journal Year: 2024, Volume and Issue: 96(18), P. 7172 - 7178

Published: April 22, 2024

Achieving sensitive detection and accurate identification of cancer cells is vital for diagnosing treating the disease. Here, we developed a logic signal amplification system using DNA tetrahedron-mediated three-dimensional (3D) nanonetworks electrochemiluminescence (ECL) subtype cells. Specially designed hairpins were integrated into tetrahedral nanostructures (DTNs) to perform catalytic hairpin assembly (CHA) reaction in presence target microRNA, forming hyperbranched 3D nanonetworks. Benefiting from "spatial confinement effect," (DTCHA) displayed significantly faster kinetics greater cycle conversion efficiency than traditional CHA. The resulting could load large amount Ru(phen)

Language: Английский

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Spatially Localized Entropy-Driven Evolution of Nucleic Acid-Based Constitutional Dynamic Networks for Intracellular Imaging and Spatiotemporal Programmable Gene Therapy

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(30), P. 20685 - 20699

Published: July 16, 2024

The primer-guided entropy-driven high-throughput evolution of the DNA-based constitutional dynamic network, CDN, is introduced. entropy gain associated with process provides a catalytic principle for amplified emergence CDN. concept applied to develop programmable, spatially localized DNA circuit effective in vitro and vivo theranostic, gene-regulated treatment cancer cells. consists tetrahedron core modified at its corners four tethers that include encoded base sequences exhibiting capacity emerge assemble into [2 × 2] Two are caged by pair siRNA subunits, blocking mute, dynamically inactive configuration. In presence miRNA-21 as primer, subunits displaced, resulting release siRNAs silencing HIF-1α mRNA fast reconfiguration CDN is, however, engineered be reconfigured miRNA-155 an equilibrated mixture enriched DNAzyme component, catalyzing cleavage EGR-1 mRNA. nanostructure stimulates enhanced permeation miRNA-triggered leads cooperative bis-gene-silencing mRNAs, selective apoptosis breast cells inhibition tumors tumor bearing mice.

Language: Английский

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Enzyme-Free Dynamic DNA Reaction Networks for On-Demand Bioanalysis and Bioimaging

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 25, 2024

ConspectusThe pursuit of in-depth studying the nature and law life activity has been dominating current research fields, ranging from fundamental biological studies to applications that concern synthetic biology, bioanalysis, clinical diagnosis. Motivated by this intention, spatiotemporally controlled in situ analysis living cells a prospective branch virtue high-sensitivity imaging key biomolecules, such as biomarkers. The past decades have attested deoxyribonucleic acid (DNA), with biocompatibility, programmability, customizable features, is competitive biomaterial for constructing high-performance molecular sensing tools. To conquer complexity wide extracellular–intracellular distribution biomarkers, it meaningful breakthrough explore high-efficiently amplified DNA circuits, which excel at operating complex yet captivating dynamic reaction networks various bioapplications. In parallel, multidimensional performance improvements nucleic including availability, detection sensitivity, reliability, are critical parameters realizing accurate cell regulation bioanalysis.In Account, we summarize our recent work on enzyme-free bioanalysis three main aspects: circuitry functional extension recognition epigenetic regulation, amplification ability improvement sensitive biomarker detection, site-specific activation systems reliable imaging. first part, designed an epigenetically responsive deoxyribozyme (DNAzyme) system intracellular gene enriches possible analyzed species chemically modifying conventional DNAzyme. For example, exquisite N6-methyladenine (m6A)-caged DNAzyme was built achieving precise FTO (fat mass obesity-associated protein)-directed regulation. addition, varieties DNAzyme-based nanoplatforms self-sufficient cofactor suppliers were assembled, subdued speed-limiting hardness cofactors live-cell applications. second developed series hierarchically assembled improve signal transduction traditional circuits. First, circuit significantly enhanced via several heterogeneously or homogeneously concatenated models. Furthermore, feedback pathway integrated into these thus dramatically increasing efficiency. Second, considering cellular environment, simplified redundancy multicomponents procedures cascaded relying minimal component merely one modular catalytic reaction, guaranteed high cell-delivering uniformity while fostering kinetics reliability. third constructed in-cell-selective endogenous-stimulated multiply recognitions, could not only eliminate leakage, but also retain its on-site multiplex amplification. Based strategy, more availability scenarios acquired These demonstrate purpose-to-concreteness engineering tailored multimolecule multiple amplification, high-gain high-reliability targeted bioanalysis. We envision network can contribute bioanalytical layouts, will facilitate progression diagnosis prognosis.

Language: Английский

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