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

Science China Chemistry, Год журнала: 2023, Номер 66(11), С. 3105 - 3115

Опубликована: Окт. 7, 2023

Язык: Английский

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Stimuli‐Responsive DNA Circuits for High‐Performance Bioimaging Application

Advanced Sensor Research, Год журнала: 2023, Номер 2(9)

Опубликована: Март 3, 2023

Abstract Probing endogenous molecules in living entities is significant to help decipher biological functions and exploit novel theranostics. DNA circuits that can recognize molecular inputs of interest transduce them into readable signal outputs an isothermal autonomous manner have been actively pursued as versatile toolkits for intracellular biosensing research. Tremendous efforts are being devoted developing integrated with high sensitivity, while spatiotemporal selectivity often overlooked the construction functional circuitry systems. This requires development stimuli‐responsive be activated on‐demand from initial sensing‐blunt state sensing‐ready under a programmable manner, achieving precise bioimaging control. In this review, overview recent advances respond particular triggers, including external physical stimuli cues, their spatiotemporally controllable applications provided. The current challenges potential solutions these future developments emerging field also discussed.

Язык: Английский

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Spatiotemporally Programmed Disassembly of Multifunctional Integrated DNAzyme Nanoplatfrom for Amplified Intracellular MicroRNA Imaging

Small, Год журнала: 2023, Номер 20(2)

Опубликована: Сен. 5, 2023

Abstract The sensing performance of DNAzymes in live cells is tremendously hampered by the inefficient and inhomogeneous delivery DNAzyme probes their incontrollable off‐site activation, originating from susceptibility to nuclease digestion. This requires development a more compact robust DNAzyme‐delivering system with site‐specific activation property. Herein, highly Zn@DDz nanoplatform constructed integrating unimolecular microRNA‐responsive DNA‐cleaving (DDz) probe requisite Zn 2+ ‐ion cofactors, amplified intracellular imaging microRNA via spatiotemporally programmed disassembly nanoparticles achieved. multifunctional simply composed structurally blocked self‐hydrolysis DDz inorganic bridge, high loading capacity, can effectively deliver initially catalytic inert into living enhanced stabilities. Upon entry acidic microenvironment cells, self‐sufficient nanoparticle disassembled release simultaneously supply cofactors. Then, endogenous microRNA‐21 catalyzes reconfiguration for generating readout signal multiply guaranteed performance. Thus, this work paves an effective way promoting DNAzyme‐based biosensing systems shows great promise clinical diagnosis.

Язык: Английский

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Simultaneous Imaging of Multiple miRNAs in Mitochondria Controlled by Fluorescently Encoded Upconversion Optical Switches for Drug Resistance Studies

Analytical Chemistry, Год журнала: 2023, Номер 95(32), С. 12152 - 12160

Опубликована: Авг. 3, 2023

Mitochondrial miRNAs (mitomiRs) are essential regulators of biological processes by influencing mitochondrial gene expression and function. To comprehensively understand related pathological treatments, simultaneous imaging multiple mitomiRs is crucial. In this study, we present a technique that enables monitoring in living cells using near-infrared (NIR) photoactivated controlled detection probe (PD-mFleU) with fluorescence-encoded error correction module nonsupervised machine learning data-processing algorithm. This method allows sensing DNA reporter can be activated NIR light after targeted localization. Multilayer upconversion nanoparticles (UCNPs) used for encoding probes correction. Additionally, the density-based spatial clustering applications noise (DBSCAN) algorithm to process analyze image. Using technique, achieved rapid situ abnormal three (miR-149, miR-590, miR-671) mt-ND1 drug-resistant cells. Furthermore, upregulating simultaneously efficiently reverted sensitive Our study provides an analytical strategy multiplex potential clinical applications.

Язык: Английский

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A High-Efficiency Autocatalysis-Oriented Cascade Circuit via Reciprocal Hug-Amplification for Assay-to-Treat Application

Analytical Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

Developing a DNA autocatalysis-oriented cascade circuit (AOCC) via reciprocal navigation of two enzyme-free hug-amplifiers might be desirable for constructing rapid, efficient, and sensitive assay-to-treat platform. In response to specific trigger (T), seven functional hairpins were designed execute three-branched assembly (TBA) three isotropic hybridization chain reaction (3HCR) events operating the AOCC. This was because new inducers reconstructed in TBA arms initiate 3HCR (TBA-to-3HCR) periodic T repeats resultantly reassembled tandem nicks polymeric nanowires rapidly activate opposite direction (3HCR-to-TBA) without steric hindrance, thereby cooperatively manipulating sustainable AOCC progress exponential hug-amplification (1:3Nn). Our experimental verifications manifested that T-dependent amplifier achieved fast input transduction efficient fluorescence readout. As predicted, flexible programming reactive hairpin species endowed repeating productive with great possibilities accessibilities graft tailored modular elements, such as G-rich AS1411 aptamers capable adopting G-quadruplex conformations (G4) readily facilitated embedding zinc(II) protoporphyrin IX (ZnPPIX), kind heme oxygenase-1 enzyme inhibitor. Thus, cascading ZnPPIX/G4 entities acted fluorescent signal reporters, photosensitizers anticancer drugs, creating an updated AOCC-based platform ultrasensitive biosensing, discernible cell imaging photodynamic therapy cancer cells. would offer paradigm advance rational integration dynamic amplifiable recycling circuits applicable bioassay theranostics.

Язык: Английский

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The Trend of Nonenzymatic Nucleic Acid Amplification: Strategies and Diagnostic Application

Precision Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 3, 2025

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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Endogenous Enzyme-Activatable Spherical Nucleic Acids for Spatiotemporally Controlled Signal Amplification Molecular Imaging and Combinational Tumor Therapy

Analytical Chemistry, Год журнала: 2023, Номер 95(39), С. 14710 - 14719

Опубликована: Сен. 20, 2023

Due to the adjustable hybridization activity, antinuclease digestion stability, and superior endocytosis, spherical nucleic acids (SNAs) have been actively developed as probes for molecular imaging development of noninvasive diagnosis image-guided surgery. However, since highly expressed biomarkers in tumors are not negligible normal tissues, an inevitable background signal inability precisely release at chosen region remain a challenge SNAs. Herein, we proposed rationally designed, endogenous enzyme-activatable functional SNA (Ep-SNA) spatiotemporally controlled amplification combinational tumor therapy. The self-assembled amphiphilic polymer micelles (SM-ASO), which were obtained by simple rapid copper-free strain-promoted azide-alkyne cycloaddition click reaction between dibenzocyclooctyne-modified antisense oligonucleotide azide-containing aliphatic polylactic acid, introduced core elements Ep-SNA. This Ep-SNA was then constructed connecting two apurinic/apyrimidinic (AP) site-containing trailing DNA hairpins, could occur via chain presence low-abundance survivin mRNA SM-ASO through complementary base pairing. Notably, AP hairpins also empowered with feasibility drug delivery. Once this intelligent nanoprobe specifically cleaved cytoplasmic human endonuclease 1 cells, three key (trailing oligonucleotide, doxorubicin) be released enable subsequent high-sensitivity cancer therapy (gene silencing chemotherapy). strategy shows great application prospects SNAs precise platform integration disease treatment can contribute basic biomedical research.

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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