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JACS Au · 2025 · IF 8.7

DNA Logic-Integrated Quantum Nanosensor for MicroRNA Diagnostics

Weiming Lin,Tao Ding,Die He,Nan Zhang,Haodong Li,Wenjian Luo,Zhongxia Wei,Min Ke,Sisi Jia,Chunhai Fan,Le Liang

Nanodiamonds (NDs) with nitrogen-vacancy (NV) centers are emerging as powerful quantum nanosensors (QNs) in biomedical applications due to their exceptional sensitivity. However, achieving optimal diagnostics performance necessitates both high sensitivity and selectivity; especially in practical biomedical settings, it remains challenging for QNs to provide quantitative analyses when multiple analytes are present. Here, we present a biosensing platform that integrates DNA logic gates (DLGs) with spin-based quantum sensing, termed DLG-QN for ultrasensitive and ultraselective diagnostics. Utilizing an AND DLG, both NDs and magnetic beads (MBs) are functionalized with hairpin DNA strands. In the presence of both miRNA-21 and miRNA-155─key biomarkers overexpressed in cancer─the hairpin DNAs undergo conformational changes that facilitate DNA-guided self-assembly of NDs and MBs, enriching the target signal. Resonant microwave modulation of ND fluorescence emission allows for high signal-to-noise ratio (SNR) detection by separating the signal from background fluorescence via spin-enhanced analysis. This platform demonstrated ultrasensitive and ultraselective detection of miRNA-21 and miRNA-155 with a limit of detection of 19.8 fM, highlighting its potential as a general biosensing strategy for precision diagnostics involving multiple biomarkers.

研究领域: 生物医学工程 · 分子诊断学 · 量子生物学
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ACS Applied Materials & Interfaces · 2025 · IF 8.2

DNA Logic Gate-Triggered Membrane Fusion for Accurately Detecting and Killing Cancer Cells

Chuanye Tang,Lei Feng,Pinghua Ling,Qiuting Wang,Wenwen Xu,Danjie Song,Yalong Qiao,Feng Gao

Accurately and sensitively identifying and killing cancer cells, especially those in deep tissues, is of paramount importance but presents significant challenges. Herein, a membrane protein and adenosine triphosphate (ATP)-driven DNA logic gate-modified liposome is designed to coat zinc peroxide (ZP) nanoparticles integrated with nanozymes (ZP/RuTe@L/DNA) to accurately identify and induce cell apoptosis in cancer cells through a reactive oxygen species (ROS)-mediated mechanism under acid conditions in cancer cells. In this system, DNA logic gate-functionalized liposomes are loaded with ZP and nanozymes, while HeLa cancer cells are functionalized with a DNA segment that is complementary to a segment of the DNA logic gate. For the DNA logic gate, a DNA aptamer was employed for membrane protein recognition, and another aptamer was used for the response of extracellular ATP. Activation of the DNA logic gate occurs only when both biomarkers are simultaneously present. Once activated, the DNA logic gate-modified liposome could hybridize with DNA segment-modified HeLa cells, leading to liposome–HeLa cell fusion and the release of ZP/RuTe into HeLa cells. Under acid conditions, ZP could decompose to release H2O2 and Zn2+, which could promote the production of •O2– and H2O2 by inhibiting the electron transport chain. Concurrently, the released RuTe exhibits glutathione (GSH) depletion and peroxidase (POD) and nicotinamide adenine dinucleotide (NADH) peroxidase-like activities, generating highly toxic hydroxyl radical (•OH), disrupting the cellular redox homeostasis, and inducing cell apoptosis. The ZP/RuTe@L/DNA system could not only accurately detect cancer cells in complex cell mixtures but also present a novel method for liposome–membrane fusion processes in drug delivery. This study presents significant potential for application in precise cancer diagnosis and therapy.

CAS / MDL: 4004-05-1 26853-31-6
研究领域: 生物化学 · 纳米医学 · 肿瘤学
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TALANTA · 2016 · IF 4.035

Thiazole orange as a fluorescent probe: Label-free and selective detection of silver ions based on the structural change of i-motif DNA at neutral pH

Bei Hua Kang,Zhong Feng Gao,Na Li,Yan Shi,Nian Bing Li,Hong Qun Luo

Silver ions have been widely applied to many fields and have harmful effects on environments and human health. Herein, a label-free optical sensor for Ag + detection is constructed based on thiazole orange (TO) as a fluorescent probe for the recognition of i-motif DNA structure change at neutral pH. Ag + can fold a C-rich single stranded DNA sequence into i-motif DNA structure at neutral pH and that folding is reversible by chelation with cysteine (Cys). The DNA folding process can be indicated by the fluorescence change of TO, which is non-fluorescent in free molecule state and emits strong fluorescence after the incorporation with i-motif DNA. Thus, a rapid, sensitive, and selective method for the detection of Ag + and Cys is developed with a detection limit of 17 and 280   nM, respectively. It is worth noting that the mechanism underlying the increase of the fluorescence of thiazole orange in the presence of i-motif structure is explained. Moreover, a fluorescent DNA logic gate is successfully designed based on the Ag + /Cys-mediated reversible fluorescence changes. The proposed detection strategy is label-free and economical. In addition, this system shows a great promise for i-motif/TO complex to analyze Ag + in the real samples.

研究领域: 分析化学 · 生物化学 · 分子生物学 · 环境科学
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TALANTA · 2016 · IF 4.035

“Molecular beacon”-hosted thioflavin T: Applications for label-free fluorescent detection of iodide and logic operations

Yan-Yun Li,Xiao-Qin Jiang,Ling-Fei Lu,Min Zhang,Guoyue Shi

In this work, we presented a simple, label-free and rapid-responsive fluorescence assay for iodide (I − ) detection based on “molecular beacon (MB)”-hosted thioflavin T (ThT), achieving a limit of detection as low as 158   nM. The proposed method exhibited very good selectivity to I − ions over other anions interference due to the strong binding force between I − ions with Hg 2+ . Upon the addition of I − ions, it would capture Hg 2+ from a T–Hg 2+ –T complex belonging to the MB-like DNA hairpin structure, which eventually quenched the initial fluorescence as output. In addition, it was successfully applied for operation of an integrated DNA logic gate system and to the determination of I − in real samples such as human urine.

CAS / MDL: 128-53-0
研究领域: 分析化学 · 生物化学 · 分子生物学 · 生物医学工程
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TALANTA · 2018 · IF 4.244

SERS detection of mercury (II)/lead (II): A new class of DNA logic gates

Qiang Zou,Xin Li,Tao Xue,Jia Zheng,Qi Su

A conceptually new class of DNA logic gates for Hg 2+ and Pb 2+ ion simultaneous detection has been constructed based on the activity of DNAzyme dependent on metal ions . For sensitive and specific detection of Hg 2+ and Pb 2+ ions, we demonstrate a surface-enhanced Raman scattering (SERS)-active platform by employing the oligonucleotide-functionalized and gold coated polystyrene microspheres (PSMPs). In this work, Hg 2+ and Pb 2+ were used as the input, and the SERS signals were the output. Hg 2+ ions were captured by a mismatched T-Hg-T bridge. Pb 2+ ions were bound to 8–17DNAzyme to break the cleavage substrate. The limit of detection (LOD) of Hg 2+ is 0.1 nmol L −1 and Pb 2+ is 1.0 nmol L −1 , which is far below the limit of 10.0 ppb (31 nmol L −1 ) and 10.0 ppm (3.02 × 10 4 nmol L −1 ) for drinking water stipulated by the World Health Organization. Additionally, this system has the potential to be ideal candidates for intelligent DNA calculator design applications. Furthermore, the designed strategy could be extended to other multiplex metal ions that can be combined with DNA molecules, and can be applied to many other fields such as environmental detection, toxin detection and liquid analysis.

研究领域: 分析化学 · 环境科学 · 生物化学 · 纳米技术
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Chemical Science · 2019 ·Vol. 10 ·期 30 ·7290-7298 · IF 9.556

A Janus-inspired amphichromatic system that kills two birds with one stone for operating a “DNA Janus Logic Pair” (DJLP) library

Daoqing Fan,Juan Wang,Erkang Wang,Shaojun Dong

Although DNA computing has exhibited a magical power across diverse areas, current DNA logic gates with different functions are always separately operated and can only produce hard-to-visualize output. The fussy/obligatory gates' redesign/reconstruction and the non-intuitive output cause the wastage of time and costs, low efficiency and practicality. Herein, inspired by the ancient Roman mythical God Janus, for the first time, we propose the concept of “DNA Janus Logic Pair” (DJLP) to classify the DNA logic gates with contrary functions into “Positive + Negative” gates (DJLP = Pos + Neg). Based on the biocatalytic property of G-quadruplex DNAzyme (G4zyme) and the luminescence quenching ability of oxidized 3,3′,5,5′-tetramethylbenzidine (OxTMB) towards the upconversion (UC) particles, we fabricated a universal amphichromatic platform that kills two birds with one stone for operating a versatile DJLP library. Different from the previous DNA logic systems, the “Pos + Neg” gates of each DJLP in this study were concomitantly achieved via the same one-time DNA reaction, which avoided the gates' redesign/reoperation and reduced the operating costs/time of the DNA gates by at least half. Besides, both the amphichromatic outputs (Visual-blue and UC luminescent-green) can be visualized under harmless-NIR, thus bringing greatly enhanced practicality to the method. Moreover, we constructed various concatenated logic circuits via logically modulating the G4zyme's biocatalytic property with glutathione, thus enabling the largely improved computing complexity. Furthermore, taking the circuit “YES-INH-1-2 decoder” as the “computing core”, we designed an “antioxidant indicator” with ratiometric logical responses that could recognize the presence of antioxidants smartly (output changed from “10” to “01”), which provided a typical prototype for potential intelligent bio-applications.

研究领域: 生物信息学 · 分子生物学 · 化学生物学 · 纳米技术
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Small Structures · 2024 · IF 13.9

A Bilingual Nanobiosensor for Cross-Category Integrated Decoding of the Beta-Site Amyloid Precursor Protein-Cleaving Enzyme 1–Aβ Oligomer Signaling Pathway

Tao Cheng,Peifen Lu,Yixi Dong,Jiabao Yu,Gang Wang,Jianwei Jiao,Peng Miao,Jin Jiao

Herein, a sequentially responsive peptide DNA bilingual nanobiosensor is developed, which allows integrated quantification of amyloid signaling pathway. In this system, upstream beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) protease and downstream Aβ oligomer (AβO) are designed as two inputs for the AND DNA logic gate. In the existence of both inputs, peptide substrate with aptamer can be sequentially cleaved, reporting electrochemical and fluorescence dual-mode outputs. In comparison with conventional single protease activity assay based on peptide nanotechnology, this strategy permits accurate diagnosis of Alzheimer's disease (AD) from normal subjects. More importantly, it can achieve distinguished diagnosis between AD and type 2 diabetes mellitus patients. This bilingual nanobiosensor is successfully applied to detect BACE1 (1–100 U mL −1 ) and AβO (5–1000 pg mL −1 ) with limit of detections as low as 0.10 U mL −1 and 0.76 pg mL −1 , respectively. Furthermore, this strategy inspires advanced nanobiosensors to target the activation of other signaling pathways, which are potential tools for future biology and medicine investigation.

CAS / MDL: 68-04-2
研究领域: 纳米技术 · 生物化学 · 分子生物学 · 诊断学 · 神经退行性疾病
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