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CHEMICAL ENGINEERING SCIENCE · 2023 · IF 4.7

Three-phase contact line confined dense nanoparticle array for high-capacity DNA synthesis

Xiao Su,Xiaoping Li,Yi Zhang,Qing Guo,Xingguo Zhang,Haixia Yu,Dachao Li

This paper presents a facile and cost-effective fabrication method of microreactor array chip for high-throughput DNA synthesis with three orders of mangnitude enhancement in synthesis capacity. Inkjet printing was used to dispense a massive droplet array of silica nanoparticle slurry on chemically-modified surface. Dense microreactor array can be simply obtained by following the procedure of three-phase contact line (TCL)-confined nanoparticle aggregating, which is dominated by the receding contact angle (RCA) of the modified substrates. Chip with RCAs greater than 90° transfers the resultant force to a lifting statu as well as enhances the inward force effect, which leading to a dense and compact packing synergistically on limited chip area. Herein, a consequential increasement in effective reaction area contributes to the significant enhancement in synthesis capacity as compared to a planar or porous substtrate. The proposed microarray chip demonstrates great prospects for both high-throughput and high-capacity DNA synthesis.

CAS / MDL: 75-12-7 7647-01-0
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Acta Biomaterialia · 2023 · IF 9.7

Cationic brush hybrid nanoparticles scavenge cell-free DNA to enhance rheumatoid arthritis treatment

Xingliang Liu,Shi Chen,Lixin Liu,Yongming Chen

Abnormally high level of cell-free DNA (cfDNA) is one of the important causes of autoimmune diseases, which aggravate the symptoms of rheumatoid arthritis (RA). Recently, the utilization of cationic polymeric nanoparticles for scavenging cfDNA has emerged as a promising therapeutic strategy for the treatment of RA. However, the intravenous introduction of cationic polymeric nanoparticles into the circulation carries a risk of dissociation, causing toxicity. To realize the potential clinical translation, we employed a series of silica particles grafted with poly(2-(dimethylamino) ethyl methacrylate) (PDMA) (SiNP@PDMA) brush, which possess adjustable PDMA content (100, 200, and 300 degree of polymerization (DP)) and particle size (50, 100, and 200 nm diameter), to selectively scavenge cfDNA in inflamed joint cavity. We demonstrate that the binding affinity for cfDNA, cytotoxicity, circulation time in vivo and retention in the inflamed joint cavity are influenced by the core-shell structure of SiNP@PDMA, ultimately impacting therapeutic efficacy. Among them, SiNP@PDMA with 100 nm size and 200 DP of PDMA exhibit enhanced accumulation and prolonged retention time in inflammatory joint cavity, resulting in superior therapeutic effect. Therefore, in this study, applying the precisely tuning size and cation content of SiNP@PDMA, we demonstrated the factors to matter the therapeutic effect of cationic nanoparticles, which deepened the understanding of the anti-inflammatory therapies based on cfDNA scavenger for RA. Statement of significance Inspired by the discovery that cfDNA would induce inappropriate immune responses to exacerbate the progress of RA, we innovatively employed SiNP@PDMA as a cfDNA scavenger to inhibit cfDNA-induced inflammation in RA. Increase in the cation content efficiently strengthened the binding between SiNP@PDMA and cfDNA, leading to an improvement in inhibitory effect of inflammation. In addition, we compared the behaviors of 50, 100 and 200 nm SiNP@PDMA in RA symptom suppression, local cfDNA scavenging and inflammation inhibition. The results demonstrated that SiNP 100 -PDMA 200 outperformed other analogues, corresponding to their more favorable distribution in inflammatory articular cavity. Together, this study revealed the structure-property relationship of cfDNA scavengers for further development of safe and effective cfDNA scavenging system.

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MICROCHIMICA ACTA · 2022 ·Vol. 189 ·期 10 ·1-11 · IF 6.408

Conductive metal–organic framework based label-free electrochemical detection of circulating tumor DNA

Liu Juan,Yang Siyi,Shen Jinhui,Fa Huanbao,Hou Changjun,Yang Mei

An ultrasensitive electrochemical biosensor was designed for the rapid label-free detection of circulating tumor DNA (ctDNA, EGFR 19 Dels for non-small cell lung cancer, NSCLC). We linked the highly conjugated tricatecholate, 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) with Ni(II) ions into the two-dimensional porous conductive metal–organic frameworks (MOFs), which is termed Ni-catecholates (Ni-CAT). Then, the AuNPs/Ni-catecholates/carbon black/polarized pencil graphite electrode (AuNPs/Ni-CAT/CB/PPGE) was obtained by electrodeposition of AuNPs on the surface of PPGE modified with Ni-CAT/CB composite materials. The AuNPs/Ni-CAT/CB/PPGE were used for label-less detection of ctDNA, with a total detection time of only 30 min. Under optimal detection conditions, the AuNPs/Ni-CAT/CB/PPGE sensor exhibited excellent detection performance with good linear response to ctDNA over a wide concentration range and the detection limit down to the femtomolar level. The sensor was applied to the determination of ctDNA in serum samples with high sensitivity. This simple, efficient, and expeditious method has practical value in liquid biopsy of ctDNA and has potential for development in early detection, treatment, and prognosis of tumors. Graphical abstract Herein, an ultrasensitive electrochemical biosensor was designed for the rapid label-free detection of ctDNA (EGFR 19 Dels for non-small cell lung cancer, NSCLC). We linked the highly conjugated tricatecholate, 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) with Ni(II) ions into the two-dimensional porous conductive metal–organic frameworks (MOFs), which is termed as Ni-catecholates (Ni-CAT). Then, the AuNPs/Ni-catecholates/carbon black/polarized pencil graphite electrode (AuNPs/Ni-CAT/CB/PPGE) was obtained by electrodeposition of AuNPs on the surface of PPGE modified with Ni-CAT/CB composite materials. The AuNPs/Ni-CAT/CB/PPGEs were used for label-less detection of ctDNA, with a total detection time of only 30 min. Under optimal detection conditions, the AuNPs/Ni-CAT/CB/PPGE sensor exhibited excellent detection performance with good linear response to ctDNA in the concentration range of 1 × 10 −15  M to 1 × 10 −6  M and with a detection limit as low as 0.32 fM. The sensor was applied for determination of ctDNA in serum samples and gave high sensitivity. This simple, efficient and expeditious method has practical value in liquid biopsy of ctDNA and has potential for development in early detection, treatment and prognosis of tumors.

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TALANTA · 2022 · IF 6.556

Optical fiber SPR biosensor based on gold nanoparticle amplification for DNA hybridization detection

Like Li,Ya-nan Zhang,Wanlu Zheng,Xuegang Li,Yong Zhao

An optical fiber SPR biosensor based on multimode fiber (MMF)- hollow core fiber (HCF)-MMF is proposed and experimentally confirmed for in situ DNA hybridization analysis. In order to improve the sensitivity of DNA hybridization detection, a sandwich model based on gold nanoparticles (AuNPs) amplification is proposed. In this model, the probe DNA (pDNA) is first modified on the optical fiber sensing area by covalent bonding, and then the biotinylated target DNA (tDNA) is modified on the AuNPs by the high affinity between biotin and streptavidin. Finally, the tDNA on the surface of the AuNPs specifically hybridizes with the pDNA on the optical fiber to form a sandwich model. The near field coupling enhancement between AuNPs and gold film and the high mass ratio of AuNPs give high sensitivity to DNA hybridization detection. Experimental results show that the sandwich-type fiber SPR sensor has a log-linear response in the DNA concentration range of 1 pM–10 nM, and the sensitivity and detection limit are 4.04 nm/log(μM) and 1pM, respectively. This is 1.44 times more sensitive than that without sandwich assay. In addition, the DNA sensor has good specificity and stability, which foreshadows its great application potential in the fields of disease diagnosis, microbial detection and environmental science.

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ANALYTICAL CHEMISTRY · 2022 · IF 8.008

High-Selectivity Single-Nucleotide Variant Capture Technology Based on the DNA Reaction Network

Weiyang Tang,Yibin Zhang,Jiachun Wang,Yi Zhao,Xiaoling Xu,Conghui Liu,Yizhen Liu,Xueji Zhang

The extremely low abundance of circulating tumor DNA in blood samples has limited the development of liquid biopsy techniques for the early diagnosis of major diseases. In this study, we demonstrate a DRN-based screening technique, SCREEN, which achieves the specific capture and enrichment of low abundance SNV nucleic acid samples without selective amplification. The SCREEN technique achieved a 108-fold increase in the abundance of single-nucleotide variant (SNV) nucleic acids from highly homologous mixtures (from 0.01% to 1.08%) and has been shown to significantly increase the abundance of SNV nucleic acids from 0.1% to 51% further through two rounds of capture. As a highly effective pre-enrichment technique, SCREEN has demonstrated the ability to enhance NGS in detecting an ultralow abundance SNV nucleic acid powerfully and has high compatibility with existing molecular diagnostic methods.

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Nano Today · 2022 · IF 18.962

Implementation of logic operations and bioanalysis based on DNA allostery-regulated nanometallic catalysis

Yuchun Guo,Jiangtao Ren,Erkang Wang

This work reports exquisite logic manipulation of nanometallic catalysis of DNA-templated silver nanoclusters (DNA-AgNCs) based on designative input-responsive DNA allostery and distinct inhibition effects of duplexes and triplexes on catalytic activity . A series of molecular logic gates (YES, OR, INHIBIT, XOR and MAJORITY) are presented, which are capable to control the catalytic activity of DNA-AgNCs in logic manners. Distinct from most of previous DNA-AgNC-based logic gates, its catalytic effect is adopted as the output signal instead of variable fluorescence , which offers a novel and robust approach for fabrication of molecular logic gate. One of the logic systems performs multiple bioanalysis of cardiac biomarkers (cardiac troponin I and myoglobin). Hence, it is worthwhile to anticipate intelligent detection of more significant disease biomarkers will be attained with the low-cost and universal platform. Moreover, the integration of programmable DNA reaction and aptamer recognition endows DNA-AgNCs catalytic specificity, which will give us hints how to devise smart DNA-functionalized nanomaterials .

CAS / MDL: 16940-66-2
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CHEMOSPHERE · 2022 · IF 8.943

Tetrachlorobisphenol A mediates reproductive toxicity in Caenorhabditis elegans via DNA damage-induced apoptosis

Yunjiang Yu,Xin Hua,Haibo Chen,Yue Yang,Yao Dang,Mingdeng Xiang

Tetrachlorobisphenol A (TCBPA), an alternative to tetrabromobisphenol A (TBBPA), is ubiquitous in the environment and could potentially impact the reproductive system of organisms. However, the mechanisms underlying TCBPA-mediated reproductive effects remain unclear. Herein, we exposed Caenorhabditis elegans ( C. elegans , L4 larvae) to TCBPA at environmentally relevant doses (0–100 μg/L) for 24 h. Exposure to TCBPA at concentrations of 1–100 μg/L impaired fertility of C. elegans , as indicated by brood size . After staining, the number of germline cells decreased in a dose-dependent manner, whereas germline cell corpses increased in exposed nematodes (10–100 μg/L TCBPA). Moreover, the expression of genes related to the germline apoptosis pathway was regulated following exposure to 100 μg/L TCBPA, indicating the potential role of DNA damage in TCBPA-induced apoptosis. Apoptosis was nearly abolished in ced-4 and ced-3 mutants and blocked in hus-1 , egl-1 , cep-1 , and ced-9 mutants. Numerous foci were detected in TCBPA (100 μg/L)-exposed hus-1::GFP strains. These results indicate that TCBPA induces hus-1 -mediated DNA damage and further causes apoptosis via a cep-1 -dependent pathway. Our data provide evidence that TCBPA causes reproductive toxicity via DNA damage-induced apoptosis.

CAS / MDL: 79-95-8
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CHINESE JOURNAL OF ANALYTICAL CHEMISTRY · 2022 · IF 1.193

Electrochemical sensor based on MoS2 nanosheets and DNA hybridization for trace mercury detection

Ri WANG,Chen-Yu XIONG,Yong XIE,Ming-Jie HAN,Yu-Hao XU,Chao BIAN,Shan-Hong XIA

Mercury ions (Hg 2+ ) are highly toxic and can cause serious harm to the environment and human health. In this study, we prepared a novel electrochemical sensor based on an electrode coated with chitosan/graphene oxide/molybdenum disulfide/Au nanoparticles (chitosan/GO/MoS 2 /AuNPs) and thymine-Hg 2+ -thymine base pair to detect trace Hg 2+ in water. This method effectively utilized the affinity of MoS 2 to immobilize deoxyribonucleic acid (DNA) on the electrode surface and enabled the amplification of the electrochemical signals detected by the sensor. The specific binding of the thymine-Hg 2+ -thymine base pair and the electrochemical activity of MoS 2 successfully reduced the detection limit of Hg 2+ and rendered it interference resistant. In the presence of Hg 2+ , a double-stranded structure was formed on the electrode after the interaction between Hg 2+ and DNA, which caused the change of the oxidation current signal of the electrode surface. The sensor showed good linearity ranging from 0.01 μg/L to 4 μg/L with a correlation coefficient of 0.991, and the limit of detection was found to be 5.8 ng/L. This portable chitosan/GO/MoS 2 /AuNPs modified electrode showed satisfactory recovery in tap water samples, thus demonstrating its potential for application in trace Hg 2+ detection.

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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2021 · IF 4.539

Reconstructed adoptive-macrophages with DNA-tetrahedron-CpG/siRNA for synergistic solid tumor immunotherapy

Jin Cheng,Shuang Wang,Qianhao Min,Jie Song,Ye Tian

Therapeutic nucleic acid delivery to solid tumors remains a challenge due to enzymatic degradation in cellular uptake and endosomal escape process as well as limited cell permeability. Herein, we reconstructed adoptive-macrophages by integrating functional DNA nanostructure-loaded nucleic acid drugs for tumor immunotherapy. The combination of functional small interfering RNAs (siRNAs) and CpG into DNA tetrahedron (DNA-tet) could induce the repolarization of M2 phenotype macrophages to antitumor M1 type, and releasing proinflammatory cytokines to kill tumor cells. The DNA tet-CpG/siRNA-loaded macrophages show excellent cellular uptake efficiency, parallel delivery capability and induce evident apoptosis and necrosis for tumor cells in vitro. In 4T1 xenograft tumor-bearing mice models, the adoptive macrophage with DNA tet-CpG/siRNA could effectively suppress the growth of subcutaneous tumors persistently and have low side effect for major organs. In summary, our proposed combination therapy of immunological macrophage and DNA-tet-CpG/siRNA will supply new ideas for solid tumor therapy.

CAS / MDL: 60-00-4
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ACS Nano · 2023 · IF 17.1

Leveraging DNA-Based Nanostructures for Advanced Error Detection and Correction in Data Communication

Ruru Gao,Xiu-Shen Wei,Zelin Chen,Aming Xie,Wei Dong

This study demonstrates the implementation of the Hamming code using DNA-based nanostructures for error detection and correction in communication systems. The designed DNA nanostructures conduct logical operations to compute check codes and identify and correct erroneous data based on fluorescence signals. The execution of intricate DNA logic operations requires individuals with specialized training. By interpretation of the fluorescence signals generated by the DNA nanostructures, binary language can be extracted, effectively protecting data security. The findings highlight the potential of DNA as a versatile platform for reliable data transmission.

CAS / MDL: 16961-25-4 68-04-2
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY · 2023 · IF 6.7

“Domino” cascade reactor based on DNA hydrogel for synergistic treatment of malignant tumor

Xiaofan Liu,Minghui Ma,Shuo Tian,Weicai Wang,Xuemei Li

The action pathways of starvation therapy and photodynamic therapy (PDT) do not exist in isolation and are usually related to tumor cell metabolism and immune regulation, which are of great significance in the treatment of malignant tumors. Here, a cancer-targeted “domino” cascade reactor is constructed for synergistic starvation therapy and amplifies photodynamic therapy by assembling hemin and glucose oxidase (GOx) into DNA hydrogel load with hypoxia-inducible factor 1α (HIF-1α) and photosensitizer chlorin e6 (Ce6). The cascade reactor has excellent biocompatibility and tumor targeting, which promotes PDT by reducing HIF-1α. At the same time, the G-quadruplex of AS1411 combined with hemin (AH) catalyzes the generation of oxygen from hydrogen peroxide to further improve the efficiency of PDT. The synergistic therapeutic effect of the cascade reactor is evaluated through in vivo and in vitro experiments, indicating that this cascade reactor has great potential advantages in the synergistic treatment of cancer.

CAS / MDL: 7727-54-0 67-68-5
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SENSORS AND ACTUATORS B-CHEMICAL · 2023 · IF 8.4

Automated and label-free detection of HIV DNA via digital microfluidics-chemiluminescence analysis

Bing Yang,Lu Shi,Qiaorong Tang,Wei Liu,Baoxin Li,Chaoyong Yang,Yan Jin

Automated and sensitive detection of nucleic acid is crucial for reliable and safe disease diagnostics because the minimum manual operation can effectively avoid sample contamination and infection risk. Herein, a sensitive, label-free and automated method was developed for detecting trace DNA by integrating digital microfluidics (DMF) with chemiluminescence (CL) detection. DMF can automatically manipulate discrete droplets. Taking advantage of sensitive and simple CL detection, DMF-CL integration can automatically and sensitively detect HIV DNA via the preset pathway. To further improve the sensitivity, on-chip exponential amplification reaction (EXPAR) was explored to produce large quantities of double-stranded DNA (dsDNA) in the presence of HIV DNA. Then, SYBR Green I (SG) intercalated into dsDNA to generate singlet oxygen upon light irradiation , which in situ oxidized potassium ferrocyanide into potassium ferricyanide . Finally, the CL reaction of potassium ferricyanide and luminol ensured the label-free, reliable and specific detection of HIV DNA in the range of 10 pM to 2 nM. Saving time-consuming and laborious manual operations, the DMF-CL integration greatly reduced the reagent consumption and avoided the contamination of DNA sample as well. Therefore, DMF-CL offers a promising and useful technology for developing automated and reliable biosensing and bioanalysis.

CAS / MDL: 521-31-3
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