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ADVANCED FUNCTIONAL MATERIALS · 2024 · IF 18.5

MicroRNA-Modified DNA Hexahedron-Induced Hepatocyte-Like Cells Integrating 3D Printed Scaffold for Acute Liver Failure Therapy

Tiantian Xue,Hongyan Wei,Fenfang Li,Yixin Zhang,Yuanyuan Jin,Yanteng Xu,Hon Fai Chan,Yingying Xu,Yin-Xiong Li,Mingqiang Li,Yu Tao

Acute liver failure (ALF) involves extensive necrosis of liver cells and severe impairment of liver function. Hepatocyte transplantation holds promise for treating ALF by swiftly supporting liver functions and promoting liver regeneration. However, the scarcity of suitable cell sources requires strategies to obtain enough functional hepatocyte-like cells (HLCs) and optimize their in vivo transplantation efficiency. A DNA hexahedral nanostructure (DHN) is developed loaded with microRNA-122 to efficiently induce hepatic differentiation of human adipose-derived mesenchymal stem cells into HLCs. These HLCs can serve as alternative hepatocyte sources, as confirmed by expression of liver-specific genes and proteins, and the restoration of liver functions. To enhance in vivo survival efficiency of HLCs, a versatile scaffold is also created by 3D printing the calcium-cross-linked mixture bioink composed of sodium alginate, gelatin, and silk fibroin with excellent ROS scavenging capabilities. The scaffold is infused with chitosan-DHN hydrogel containing HLCs for tissue engineering orthotopic transplantation in CCl 4 -induced ALF mice. The transplanted composite scaffold-HLCs successfully repair tissue necrosis in the liver injury area of mice and regulate expressions of genes and proteins associated with inflammation, oxidative stress, and hepatocyte function. Collectively, this study offers a novel approach and strategy for identifying alternative hepatocyte sources and treating ALF.

✓ 已验证 DOI 高影响因子
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MICROCHEMICAL JOURNAL · 2025 · IF 5.1

An electrochemical aptasensor for sensitive kanamycin detection using an Nb.BbvCI-driven DNA walker-based signal amplification strategy

Yaoting Mou,Lu Han,Yanhao Yin,Yuhang Tian,Jianghua Liu,Yanqing Xu,Dongfei Chen,Yemin Guo,Xia Sun,Falan Li,Yanfang Wu

In this study, an electrochemical aptasensor dedicated to the sensitive detection of kanamycin (KAN) was constructed based on an Nb. Bbv CI-driven DNA walker-enabled signal amplification strategy. The sensor employed a gold electrode modified with polyethyleneimine-wrapped, nitrogen-doped multi-wall carbon nanotubes decorated with gold nanoparticles (N-MWCNTs-PEI-AuNPs). This composite was used to modify the gold electrode, providing an enhanced conductive interface and increasing the specific surface area for aptasensor construction. Meanwhile, a zirconium-based metal-organic framework decorated with gold nanoparticles (AuNPs@NH₂-UiO-66) was used both as an electrocatalyst and as a carrier for hairpin DNA (HP2), exhibiting strong catalytic activity toward the redox mediator thionine. In differential pulse voltammetry measurements, at the surface of the electrode, thionine undergoes a reversible, pH-dependent two-electron/two-proton transfer process at approximately −0.25 V on the electrode surface, generating a well-defined reduction current that serves as the analytical signal. Upon addition of KAN, the aptamer selectively binds to the analyte and dissociates from its complementary DNA (cDNA). The freed cDNA subsequently hybridizes with HP2 anchored on AuNPs@NH₂-UiO-66, thereby activating the Nb. Bbv CI-driven DNA walker, catalyzing the site-specific cleavage of HP2 and releasing multiple AuNPs@NH₂-UiO-66 labels. These released probes then hybridize with the captured hairpin DNA (HP1) fixed on the N-MWCNTs-PEI-AuNPs-modified gold electrode. The synergistic electrocatalytic effects of NH₂-UiO-66 and AuNPs significantly accelerate the electron transfer kinetics of thionine, leading to amplified voltammetric current responses that correlate proportionally with KAN concentration. The aptasensor demonstrated highly sensitive performance, including a linear detection range of 10 pM to 5 μM and a detection limit of 1.65 pM and a quantitation limit of 5.46 pM. The aptasensor also showed satisfactory selectivity and reproducibility and was successfully applied for KAN determination in real milk samples. This approach provides a robust signal amplification strategy and offers a promising tool for the rapid and sensitive detection of KAN in real-world samples.

CAS / MDL: 13472-35-0 9002-98-6
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CHEMISTRY-A EUROPEAN JOURNAL · 2025 · IF 3.7

A Ruthenium(II)-DNA Nanophotosensitizer for cGAS-STING-Mediated Photodynamic Immunotherapy Against Hypoxic Cisplatin-Resistant Tumor Cells

Fa Wang,Zhiyang Wang,Shuqi Huang,Jinrong Yang,Yu Chen,Hui Chao

Graphical A convenient strategy by synergistic delivering DNA and DNA photocleavage agents to tumor cells was developed for effective photodynamic immunotherapy under hypoxia. Plasmid DNAs intercalated with Ru(II) complexes were encapsulated in liposomes to create nano-photosensitizers. Upon light exposure, the ruthenium complex photo-cleavages DNA. The DNA fragments specifically stimulate the cGAS-STING pathway and induce immunogenic death. This study presents a convenient strategy for photodynamic immunotherapy against cisplatin-resistant tumor cells under hypoxia.

CAS / MDL: 14898-67-0
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SENSORS AND ACTUATORS B-CHEMICAL · 2025 · IF 7.7

Nucleic acid-responsive DNA functionalized Fe3O4@Zr-MOF/GOx colorimetric probe for ultrasensitive detection of Salmonella typhimurium

Qing Kang,Tong Lin,Jingbo Jiao,Yidi Liu,Yurong Guo,Chenjing Ma,Xinjun Du,Shuo Wang

Salmonella typhimurium ( S. typhimurium ) contamination has become the main source of foodborne diseases and has substantial effects on human well-being. Herein, we present a nucleic acid-responsive colorimetric biosensor for ultrasensitive detection of S. typhimurium , integrating a multifunctional Fe 3 O 4 @Zr-MOF/GOx nanoprobe with exponential amplification reaction (EXPAR). The system integrates glucose oxidase (GOx) encapsulated within a Zr-based metal-organic framework (Zr-MOF) modified with magnetic Fe 3 O 4 nanoparticles. In the presence of S. typhimurium , the EXPAR reaction is triggered, and the controlled release of GOx is achieved by DNA strand displacement. The detection mechanism leverages GOx-catalyzed glucose oxidation to generate H 2 O 2 , which oxidizes 3,3’,5,5’-tetramethylbenzidine (TMB) for colorimetric signal readout. The biosensor demonstrates high specificity for S. typhimurium , with a detection limit of 2.26 CFU mL⁻¹ , and practical applicability in spiked milk samples, achieving recoveries of 89.6–111.5 %. The strategy employing stimuli-responsive DNA/MOF composites demonstrated significant potential in food quality monitoring and analysis.

CAS / MDL: 7727-54-0 79-06-1
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY · 2020 ·Vol. 412 ·期 11 ·2413-2421 · IF 3.637

Polysaccharide-enhanced ARGET ATRP signal amplification for ultrasensitive fluorescent detection of lung cancer CYFRA 21-1 DNA

Wang Xia,Zhang Yawen,Zhao Liying,Wang Dazhong,Yang Huaixia,Kong Jinming

An ultrasensitive fluorescence biosensor for detecting cytokeratin fragment antigen 21-1 (CYFRA 21-1) DNA of non-small cell lung carcinoma (NSCLC) is designed using polysaccharide and activator regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) signal amplification strategy. Thiolated peptide nucleic acid (PNA) is fixed on magnetic nanoparticles (MNPs) by a cross-linking agent and hybridized with CYFRA 21-1 DNA. Hyaluronic acid (HA) is linked to PNA/tDNA heteroduplexes in the form of carboxy-Zr 4+ -phosphate. Subsequently, multiple 2-bromo-2-methylpropionic acid (BMP) molecules are linked with HA to initiate ARGET ATRP reaction. Finally, a large number of fluorescein o-acrylate (FA) monomers are polymerized on the macro-initiators, and the fluorescence signal is significantly amplified. Under optimal conditions, this biosensor shows a significant linear correlation between the fluorescence intensity and logarithm of CYFRA 21-1 DNA concentration (0.1 fM to 0.1 nM), and the limit of detection is as low as 78 aM. Furthermore, the sensor has a good ability to detect CYFRA 21-1 DNA in serum samples and to recognize mismatched bases. It suggests that the strategy has broad application in early diagnosis by virtue of its high sensitivity and selectivity. A novel and highly sensitive fluorescence biosensor for quantitatively detecting CYFRA 21-1 DNA via dual signal amplification of hyaluronic acid and ARGET ATRP reaction was developed. This proposed method has a low detection limit, wide detection range, high selectivity, and strong anti-interference.

CAS / MDL: 109-89-7 2052-01-9
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY · 2017 ·Vol. 409 ·期 29 ·6821-6829 · IF 3.431

Sensitive electrochemical detection of DNA damage based on in situ double strand growth via hybridization chain reaction

Liu Misha,Xu Jinjin,Yang Fan,Gu Yifan,Chen Huan,Wang Ying,Li Fengting

Detection of DNA damage caused by ∙OH or radiation has led to rapidly growing interest in the fields of drug development, biochemistry, clinic diagnostics, and environmental evaluation. Electrochemical methods have been applied for DNA damage detection because of their fast and sensitive response. However, most of the electrochemical methods for DNA damage detection commonly require immobilization of the strands on the electrode surface. In the present work, sensitive electrochemical monitoring of DNA damage was realized successfully on the basis of in situ DNA chain growth by use of a hybridization chain reaction (HCR) technique. By use of [Ru(NH 3 ) 6 ] 3+ as the signal probe and the Fenton reaction as the ∙OH generator, ultrasensitive detection of DNA damage induced by ∙OH was realized successfully through differential pulse voltammetry with a linear relationship of ∙OH concentration from 15 to 750 pM and a detection limit of 12 pM. Furthermore, environmental DNA-damaging UV light was tested as the lesion source to demonstrate the practicability and reliability of the proposed HCR-based amplified signal method for DNA damage detection. By integrating the HCR technique with an electrochemical method, we provide a promising alternative approach to extend the applications of electrochemical methods in bioanalytical detection of DNA damage. Sensitive electrochemical monitoring of DNA damage has been realized successfully on the basis of in situ DNA chain growth by use of hybridization chain reaction (HCR). Detection of DNA damage caused by ∙OH was realized successfully through differential pulse voltammetry with a linear relationship of ∙OH concentration from 15 to 750 pM and a detection limit of 12 pM

CAS / MDL: 1633-78-9
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BIOMEDICINE & PHARMACOTHERAPY · 2021 · IF 6.53

Development and biological evaluation of AzoBGNU: A novel hypoxia-activated DNA crosslinking prodrug with AGT-inhibitory activity

Qi Liu,Xiaoli Wang,Jun Li,Jiaojiao Wang,Guohui Sun,Na Zhang,Ting Ren,Lijiao Zhao,Rugang Zhong

Chloroethylnitrosoureas (CENUs) are an important family of chemotherapies in clinical treatment of cancers, which exert antitumor activity by inducing the formation of DNA interstrand crosslinks (dG-dC ICLs). However, the drug resistance mediated by O 6 -alkylguanine-DNA alkyltransferase (AGT) and absence of tumor-targeting ability largely decrease the antitumor efficacy of CENUs. In this study, we synthesized an azobenzene-based hypoxia-activated combi-nitrosourea prodrug, AzoBGNU, and evaluated its hypoxic selectivity and antitumor activity. The prodrug was composed of a CENU pharmacophore and an O 6 -benzylguanine ( O 6 -BG) analog moiety masked by a N , N -dimethyl-4-(phenyldiazenyl)aniline segment as a hypoxia-activated trigger, which was designed to be selectively reduced via azo bond break in hypoxic tumor microenvironment, accompanied with releasing of an O 6 -BG analog to inhibit AGT and a chloroethylating agent to induce dG-dC ICLs. AzoBGNU exhibited significantly increased cytotoxicity and apoptosis-inducing ability toward DU145 cells under hypoxia compared with normoxia, indicating the hypoxia-responsiveness as expected. Predominant higher cytotoxicity was observed in the cells treated by AzoBGNU than those by traditional CENU chemotherapy ACNU and its combination with O 6 -BG. The levels of dG-dC ICLs in DU145 cells induced by AzoBGNU was remarkably enhanced under hypoxia, which was approximately 6-fold higher than those in the AzoBGNU-treated groups under normoxia and those in the ACNU-treated groups. The results demonstrated that azobenzene-based combi-nitrosourea prodrug possessed desirable tumor-hypoxia targeting ability and eliminated chemoresistance compared with the conventional CENUs.

✓ 已验证 DOI PubMed 高影响因子
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BIOORGANIC CHEMISTRY · 2020 · IF 4.831

Synthesis, docking studies and antitumor activity of phenanthroimidazole derivatives as promising c-myc G-quadruplex DNA stabilizers

Qiong Wu,Yue Song,Ruotong Liu,Rui Wang,Wenjie Mei,Weiming Chen,Huanglan Yang,Xicheng Wang

Phenanthroimidazole derivatives containing phenanthroline and imidazole heterocyclic aromatic rings are effective agents to inhibit tumor cell growth. Herein, halogen element-modified imidazo[4,5 f ][1,10]phenanthroline derivatives 1–6 ( 1 , 4-fluorophenyl; 2 , 4-chlorophenyl; 3 , 4-bromobenyl; 4 , 2,3-dichlorophenyl; 5 , 3,4-dichlorophenyl; and 6 , 2,4-dichlorophenyl) were synthesized, and their antitumor activities were investigated. All of the compounds, especially 4 , exhibited an excellent inhibitory effect against nasopharyngeal carcinoma CNE-1 cells. This effect was better than that of doxorubicin. Compound 4 also markedly blocked the proliferation of the CNE-1 cells in a zebrafish xenograft model. The antitumor mechanisms might be attributed to apoptosis induction, which triggered ROS-mediated DNA damage and generated mitochondrial dysfunction by stabilizing c-myc G-quadruplex DNA structure. Results indicated that phenanthroimidazole derivatives could act as promising anticancer agents.

✓ 已验证 DOI PubMed 高影响因子
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Nanoscale · 2018 ·Vol. 10 ·期 14 ·6611-6619 · IF 7.233

Combining gold nanoparticle antennas with single-molecule fluorescence resonance energy transfer (smFRET) to study DNA hairpin dynamics

Jinyong Hu,Meiyan Wu,Li Jiang,Zhensheng Zhong,Zhangkai Zhou,Thitima Rujiralai,Jie Ma

The association of a plasmonic nano-antenna with single-molecule FRET technique presents new prospects to investigate the dynamics of biological molecules. However, the presence of a plasmonic nano-antenna significantly modifies the FRET rate and efficiency; this makes its applicability to the prevalent single-molecule FRET experiments unclear. Herein, using gold nanoparticle antennas of different sizes and DNA hairpins labelled with FRET pairs (Cy3 and Cy5) as the model system, we performed experiments to study the folding dynamics of single DNA hairpins at various salt concentrations. Our results indicate that gold nanoparticle antennas can enhance single-molecule fluorescence of Cy3 and Cy5 up to 3–5 folds, substantially reduce the FRET efficiency, and alter the obtained FRET efficiency histograms. However, the folding dynamics of DNA hairpins remains unaffected, and the correct kinetic and dynamic information can still be extracted from the seriously modified FRET efficiencies. Therefore, our experiments demonstrate the feasibility and compatibility for applying plasmonic nano-antennas to the mostly used single-molecule FRET assays, which provide a broad range of possibilities for the future applications of these nano-antennas in studying various essential biological processes.

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ANALYTICA CHIMICA ACTA · 2021 · IF 6.558

Fluorometric detection of cancer marker FEN1 based on double-flapped dumbbell DNA nanoprobe functionalized with silver nanoclusters

Bingzhi Li,Peng Zhang,Bin Zhou,Siying Xie,Anqi Xia,Tiying Suo,Shuang Feng,Xing Zhang

Flap endonuclease 1 (FEN1), a ubiquitous enzyme involved in DNA repair and replication, is overexpressed in highly proliferative cancer cells. FEN1 has been recognized as a promising diagnostic marker of cancers; however, very few analytical techniques have been developed for the convenient detection of FEN1. To realize the simplified quantification of FEN1, we developed a FEN1-responsive fluorescent nanoprobe based on DNA-silver nanoclusters (DNA-AgNCs). The nanoprobe was rationally designed with a double-flapped dumbbell conformation, where its 5′ flap was produced with DNA-AgNCs, and the 3′ flap was elongated by a guanine-rich enhancer sequence (GRS). Rigidified by the DNA scaffold, DNA-AgNCs and the GRS are in close proximity, resulting in high fluorescence because of the GRS-induced activation of DNA-AgNCs. Upon the addition of FEN1, the 5’ flap of the nanoprobe is cleaved due to the structure-specific endonuclease activity of FEN1. This cleavage released the DNA-AgNCs from the nanoprobe, broke the proximity between DNA-AgNCs and the GRS, and caused decreased fluorescence. This nanoprobe can be applied in the sensitive detection of FEN1 with a detection limit of 40 fM, and it showed high specificity for the monitoring of FEN1 in clinical samples. As the first attempt to develop biosensors targeting FEN1 based on DNA-AgNCs, this work provided a potent platform for monitoring FEN1 and screening FEN1 inhibitors.

✓ 已验证 DOI PubMed 高影响因子
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MICROCHIMICA ACTA · 2013 ·Vol. 181 ·期 3 ·471-477 · IF 3.434

Electrochemical immunoassays for the detection the activity of DNA methyltransferase by using the rolling circle amplification technique

Xu Zhenning,Yin Huanshun,Tian Zhengbin,Zhou Yunlei,Ai Shiyun

We report on an electrochemical method for the determination of the activity of the enzyme methyltransferase (MTase). The methyl-binding domain-1 protein was applied to recognize symmetrically methylated cytosine in CpG (-C-phosphate-G-) islands of ds-DNA which then specifically bind to anti-His tag antibody. Hyperbranched rolling circle amplification (RCA) was used to improve sensitivity. When the dsDNA was treated with M.Sss I methyltransferase, the sequence 5′-CCGG-3′ was methylated and recognized by the methyl binding protein. In turn, the anti-His tag, biotinylated IgG, streptavidin and biotinylated oligonucleotide were captured successively on the surface of an electrode. Subsequently, the RCA reaction was initiated and streptavidin-labeled alkaline phosphatase immobilized on the surface of the electrode. ALP was able to catalyze the hydrolysis of 1-naphthyl phosphate to form 1-naphthol at pH 9.8. The oxidation peak current of 1-naphthol was used to monitor the methylation process. The response obtained by differential pulse voltammetry was linearly related to the concentration of M. Sss I MTase in the range from 0.1 to 40 unit mL −1 , and the detection limit was 0.03 unit mL −1 (at an SNR of 3). The inhibitory action of paclitaxel on the activity of M.Sss I MTase also was investigated. An electrochemical immunosensing method is described for the detection of DNA methylation, assaying DNA methyltransferase activity by combining the rolling circle amplification technique.

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SENSORS AND ACTUATORS B-CHEMICAL · 2015 · IF 4.097

Electrochemical biosensor for DNA methyltransferase detection based on DpnI digestion triggering the formation of G-quadruplex DNAzymes

Pei Liu,Min Liu,Hunshun Yin,Yunlei Zhou,Shiyun Ai

Aberrant DNA methylation, which is caused by the abnormal level of DNA methyltransferase (MTase), has been considered associated with a growing number of human diseases. Although there are various methods paying close attention to DNA methyltransferase (MTase) detection, most of them are generally complex and expensive. Here, a simple electrochemical strategy for sensitive detection of DNA methyltransferase (MTase) and inhibitor screening based on DpnI digestion triggering the formation of G-quadruplex DNAzymes has been developed. In this paper, a probe richness of guanine (G) was first self-assembled on the surface of the electrode through Au–S bond and then hybridized with the complementary DNA. Without DNA methylation, G-quadruplex DNAzymes cannot be formed due to the double helix structure and a weak electrochemical response can be observed. On the contrary, an obvious enhancement of the electrochemical response can be achieved after the cleavage of the methylated double-strand DNA by DpnI since G-quadruplex DNAzymes can be obtained, which catalyze the oxidation of hydroquinone by H 2 O 2 with the assistance of the cofactor hemin. This method is under a detection limit of 0.96   U/mL and can monitor the change of DNA methylation level selectively. Moreover, RG108 was selected as a representative inhibitor for studying the inhibition activity of DNA MTase.

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