ACS Applied Bio Materials
·
2020
·
IF 0
Yao Jiang,Xiangjuan Kong,Yanxialei Jiang,Wenjing Zhao,Huimin Zhou,Shusheng Zhang
The design of DNA nanodevices has attracted broad attention in detecting specific targets and targeted drug delivery capacities of tumor cells. Here, we report the facile fluorometric method of dual-targeting DNA nanodevices for base excision repair (BER) regulates adenosine triphosphate (ATP) in situ imaging and tumor therapy that can counteract the mutagenic effects of uracil (U) on ATP aptamer based on the binding of U-containing damaged ATP aptamer. We prove that the DNA nanodevices not only effectively deliver the aptamer probe and tumor therapy but also able to analyze the overexpression of APE1 and uracil-DNA glycosylases (UDG) in the BER pathway via ATP in situ imaging in tumor cells. Therefore, the DNA nanodevices of the BER pathway provide the potential for tumor theranostics.
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PubMed
Theranostics
·
2020
·
IF 8.579
Yuwei Li,Shuzhen Yue,Jingyu Cao,Chengzhan Zhu,Yixiu Wang,Xin Hai,Weiling Song,Sai Bi
Chemo-gene therapy is an emerging synergetic modality for the treatment of cancers. Herein, we developed pH-responsive multifunctional DNA nanomicelles (DNMs) as delivery vehicles for controllable release of doxorubicin (Dox) and anaplastic lymphoma kinase (ALK)-specific siRNA for the chemo-gene synergetic therapy of anaplastic large cell lymphoma (ALCL). Methods: DNMs were synthesized by performing in situ rolling circle amplification (RCA) on the amphiphilic primer-polylactide (PLA) micelles, followed by functionalization of pH-responsive triplex DNA via complementary base pairing. The anticancer drug Dox and ALK-specific siRNA were co-loaded to construct Dox/siRNA/DNMs for chemo-gene synergetic cancer therapy. When exposed to the acidic microenvironment (pH below 5.0), C-G·C + triplex structures were formed, leading to the release of Dox and siRNA for gene silencing to enhance the chemosensitivity in ALCL K299 cells. The chemo-gene synergetic anticancer effect of Dox/siRNA/DNMs on ALCL was evaluated in vitro and in vivo . Results: The pH-responsive DNMs exhibited good monodispersity at different pH values, good biocompatibility, high drug loading capacity, and excellent stability even in the human serum. With the simultaneous release of anticancer drug Dox and ALK-specific siRNA in response to pH in the tumor microenvironment, the Dox/siRNA/DNMs demonstrated significantly higher treatment efficacy for ALCL compared with chemotherapy alone, because the silencing of ALK gene expression mediated by siRNA increased the chemosensitivity of ALCL cells. From the pathological analysis of tumor tissue, the Dox/siRNA/DNMs exhibited the superiority in inhibiting tumor growth, low toxic side effects and good biosafety. Conclusion: DNMs co-loaded with Dox and ALK-specific siRNA exhibited significantly enhanced apoptosis of ALCL K299 cells in vitro and effectively inhibited tumor growth in vivo without obvious toxicity, providing a potential strategy in the development of nanomedicines for synergetic cancer therapy.
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高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2020
·
IF 7.1
Qingqing Zhang,Dandan Hu,Tianyu Zhan,Yufang Hu,Zhiyong Guo,Sui Wang
A novel Medusa electrochemiluminescence (ECL) immunosensor for quantitative detection of histone acetyltransferase (HAT p300) is designed and built well based on magnetic gold nanoparticles (Au-Fe 3 O 4 NPs), DNA nanonets and terminal deoxynucleotidyl transferase (TdT)-triggered renascent DNAs containing abundant A and T (named as AT-dsDNAs). Firstly, Au-Fe 3 O 4 NPs and substrate peptides are coated with the bare electrode surface one after the other. As the acetylation reaction happens, DNA nanonets, which are synthesized via Y-shape DNA (as building block) and acetyl antibody (Ab Ac )-grafted dsDNA (as crosslinker), are attached on the electrode surface. Next, AT-dsDNAs are formed under NaCl condition by TdT catalysis, in where deoxyadenosine triphosphate (dATP) and deoxythymidine triphosphate (dTTP) (half and half) can be added ceaselessly to countless 3′−OH of DNA nanonets. Abundant Ru(phen) 3 2+ molecules, which can be integrated well into high-level DNA nanomaterials above, serve as ECL luminophore in our biosensing. Only being HAT p300, an outstanding ECL response occurs favorably, and a detection limit of 0.0029 nM is acquired with a linear response in the range of 0.006–60 nM. The Medusa immunosensor with improved sensitivity presents a promising and possible widely use for the HATs-relevant clinical study and drug development.
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高影响因子
TRANSITION METAL CHEMISTRY
·
2020
·Vol. 45
·期 7
·493-500
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IF 1.366
Yang Xinda,Gu Shunxin,Jiang Qin,Wang Yanqing,Wang Daqi,Shi Pengfei
Abstract A Cu(II) complex [Cu 2 (phen) 2 (NAB) 2 (HO)] n (phen = 1, 10-phenanthroline and NABH = p -N, N-(2-hydroxyethyl)amino benzoic acid) was synthesized, and its structure was confirmed by X-ray diffraction. The structure of the complex appeared to be clamp-like, in which Cu(II) atoms adopt distorted square pyramidal geometry. Each Cu(II) is coordinated by two nitrogen atoms in phen ligand and two carboxyl oxygen atoms from each of the two NABH ligands. The clamp-like coordination units are bridged by adjacent hydroxyethyl groups into infinite 1D chain, which are further linked by extensive O···H hydrogen bonds and π–π interactions to form 3D networks. The titled complex displayed weak double-stranded DNA interaction activity. Spectroscopic and theoretical simulation results indicated that the complex attached onto DNA surface through hydrogen bonding with base pairs. Graphic abstract A novel benzoic acid derivative with two extremity hydroxyethyl groups was designed and used as auxiliary ligand to synthesize mixed coordinating clamp-like Cu(II)-phenanthroline complex. Hydrogen bonding played crucial role in bridging the clamps into infinite 1D chain and also the DNA complex interaction mode.
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高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2020
·
IF 3.232
Na Li,Xing Hu,Junhui Pan,Ying Zhang,Deming Gong,Guowen Zhang
4–Octylphenol is an endocrine disruptor , belonging to environmental estrogens. It can be enriched in the human body through the food chain and may harm human health. Herein, we used a variety of spectroscopic techniques, molecular docking, and gel electrophoresis to study the interaction of 4–octylphenol and ctDNA . It was found that the mechanism of ctDNA quenching the endogenous fluorescence of 4–octylphenol was static quenching, and formed a complex. The negative enthalpy change (Δ H °), entropy change (Δ S °) and Gibbs free energy (Δ G °) have shown that 4–octylphenol and ctDNA spontaneously bind together under the action of hydrogen bonds and van der Waal's force . Viscosity, melting temperature and iodide quenching experiments showed that 4–octylphenol acted on the groove of ctDNA. Insignificant change in circular dichromism spectra further confirmed this binding mode. The binding sites and groups for 4–octylphenol and ctDNA interaction were identified by molecular docking. Gel electrophoresis found that 4–octylphenol at high concentrations caused DNA cleavage. Above findings may lay a theoretical foundation for understanding the toxicity mechanism of 4–octylphenol.
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PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2020
·
IF 7.1
Yunfeng Sun,Shuang Li,Ruipeng Chen,Pian Wu,Jun Liang
The T-2 toxin is generated as a secondary metabolite by various species of Fusarium that are found extensively in barley, wheat, maize, and oats; consequently, the development of methods that can rapidly and efficiently detect this toxin is vital. Herein, we report on a novel and highly sensitive method based on DNA hydrogels and etched gold nanorods (AuNRs) to detect the T-2 toxin. The T-2 toxin aptamer acts as a cross-linking agent for a hydrogel in which horseradish peroxidase (HRP) is uniformly embedded. The target T-2 toxin binds to the aptamer, causing the hydrogel to collapse and release the embedded HRP, which catalyzes the reaction of H 2 O 2 with KI to produce I 2 that etches the AuNRs. The UV spectrum of the AuNRs is blue-shifted following etching; this shift is proportional to the T-2-toxin content. This method offers a low limit of detection (0.87 pg mL −1 ), low limit of quantification (2.90 pg mL −1 ), and wide detection range (0.01–10000 ng mL −1 ). Moreover, coffee, corn, and soybean were assayed using the optimized method. The approach offers good recoveries and relative standard deviations of 93.72–103.07 % and 3.87–7.07 %, respectively. The total assay time was 1.5 h. Thus, the new method is promising as an ultrasensitive assay for detecting various small molecules in complex matrices.
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高影响因子
ACS Sensors
·
2020
·
IF 7.333
Dandan Zhao,Haoran Tang,Hao Wang,Cheng Yang,Yongxin Li
The nanopore-based technique is a useful tool for single-molecule sensing and characterization. In this work, we have developed a new DNA-functionalized gold-modified nanopore, and analytes can induce the conformational switch of i-motif DNA formed on the inner surface of the nanopore. i-Motif DNA structure can be formed in the presence of silver ions (Ag+), which will result in the change in surface charge and structure of the nanopore tip and ion current rectification (ICR) ratio. The i-motif DNA structure on nanopore surface will be destroyed after the addition of glutathione (GSH) due to the strong interaction of Ag–S bond, which results in the recovery of surface charge, steric hindrance, and ICR ratio. This analyte-triggered conformational switch of i-motif DNA can help us deeply understand the DNA technology inside single nanopore and will benefit the possible applications in an ultrasensitive detection and biological/chemical analysis.
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高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Yanzi Yan,Huiyi Liang,Xingliang Liu,Lixin Liu,Yongming Chen
Abnormal high level of cell free DNA (cfDNA) triggers chronic inflammation to exacerbate psoriasis symptoms. Scavenging cfDNA by topical cationic polymeric nanoparticles has been certified as an effective therapeutic strategy for treating psoriasis. However, cationic cfDNA scavengers have a great potential risk to organs after entering systemic circulation through skin barrier. For better transformation to clinical application, herein a series of poly(2-(dimethylamino)ethyl methacrylate) (PDMA) grafted hairy silica particles (cSPs) with tunable PDMA length and particle size are applied to scavenge cfDNA in dermis. We reveal that the structure of cSPs correlates with the permeation ability across stratum corneum, retention time in dermis, binding affinity to cfDNA, and toxicity tolerance, which in turn affect the therapeutic effect. Especially, the cSPs of 700 nm show more accumulation and longer retention in psoriatic lesions, leading to excellent treatment results. They also outperform the cSPs of 200 nm at a lower administration frequency. Thus, we address the issues of size, cationic content of cSPs to open a potential new avenue to topically treatment of psoriasis by targeting cfDNA in dermis.
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高影响因子
ANALYTICAL CHEMISTRY
·
2021
·
IF 6.986
Jia-Yang He,Xin Shang,Chun-Li Yang,Si-Yu Zuo,Ruo Yuan,Wen-Ju Xu
Exploring the ratiometric fluorescence biosensing of DNA-templated biemissive silver nanoclusters (AgNCs) is significant in bioanalysis, yet the design of a stimuli-responsive DNA device is a challenge. Herein, using the anti-digoxin antibody (anti-Dig) with two identical binding sites as a model, a tweezer-like DNA architecture is assembled to populate fluorescent green- and red-AgNCs (g-AgNCs and r-AgNCs), aiming to produce a ratio signal via specific recognition of anti-Dig with two haptens (DigH). To this end, four DNA probes are programmed, including a reporter strand (RS) dually ended with a g-/r-AgNC template sequence, an enhancer strand (ES) tethering two same G-rich tails (G18), a capture strand (CS) labeled with DigH at two ends, and a help strand (HS). Initially, both g-AgNCs and r-AgNCs wrapped in the intact RS are nonfluorescent, whereas the base pairing between RS, ES, CS, and HS resulted in the construction of DNA mechanical tweezers with two symmetric arms hinged by a rigid “fulcrum”, in which g-AgNCs are lighted up due to G18 proximity (“green-on”), and r-AgNCs away from G18 are still dark (“red-off”). When two DigHs in proximity recognize and bind anti-Dig, the conformation switch of these tweezers resultantly occurs, taking g-AgNCs away from G18 for “green-off” and bringing r-AgNCs close to G18 for “red-on”. As such, the ratiometric fluorescence of r-AgNCs versus g-AgNCs is generated in response to anti-Dig, achieving reliable quantization with a limit of detection at the picomolar level. Based on the fast stimulated switch of unique DNA tweezers, our ratiometric strategy of dual-emitting AgNCs would provide a new avenue for a variety of bioassays.
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高影响因子
ANALYST
·
2019
·Vol. 144
·期 21
·6313-6320
·
IF 4.019
Xi Chen,Ya Wang,Junjun Zhang,Yuzhong Zhang
In this study, we report a metallobioassay for ultrasensitive electrochemical detection of prostate-specific antigen (PSA) based on DNA hybridization chain reaction (HCR) for amplifying the signal, which is derived from silver nanoparticles (Ag NPs) on DNA concatemers. The assay mainly consists of primary antibody (Ab1), secondary antibody (Ab2) with primer, and a signal probe. In the presence of PSA, a sandwich structure with DNA concatemers was formed, and numerous Ag NPs were loaded on the DNA concatemers, resulting in a strong signal, which appeared within the applied potential (−0.2 V to 0.3 V) in the phosphate-buffered saline (PBS). Differential pulse voltammetry (DPV) was employed to evaluate the analytical performance. Under optimal conditions, the DPV peak current of Ag NPs at about +0.09 V (vs. SCE) increased linearly as the logarithm of PSA concentration increased from 0.1 pg mL−1 to 75 ng mL−1, and the detection limit of PSA was estimated to be 0.033 pg mL−1 at the signal to noise ratio of 3. In addition, the assay was evaluated with human serum samples, and satisfying results were obtained, indicating that the assay can achieve PSA detection in the serum sample.
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高影响因子
LANGMUIR
·
2019
·
IF 3.683
Sihui He,Jiantao Yu,Fangfang Wang,Leilei Tian
Intracellular pH is a vital parameter which can reflect the physiological process, and the detection of intracellular pH with a high signal-to-noise ratio (SNR) remains a challenge. Compared to pH biosensors based on a single-wavelength signal, it is much easier to obtain better sensitivity and higher SNR from the biosensors by two-wavelength ratiometric signals. In this study, we used DNA-grafted graphene oxide (GO) to ratiometrically detect intracellular pH ranging from basic to acidic. A high SNR with a 35-fold difference in the ratiometric output has been achieved through careful optimization: (1) A high DNA conjugation yield of 45% has been gained through utilizing the partial double-stranded assembly strategy. (2) Herring sperm DNA (HSD) plays an important role in improving the sensitivity of the nanosystem by purifying and passivating the surface of GO; therefore, the concentration of HSD has been optimized to pursue the most sensitive ratiometric response. Apart from the ultrahigh SNR, fabricated GO-AR-Cy5/IFO-Cy3 exhibited excellent stability and biocompatibility in biological environments. Further experiments demonstrated that the nanosystem worked well in live cells in response to pH changes. It is possible to distinguish small pH differences and realize quantitative detection based on ratiometric fluorescence imaging by laser scanning confocal microscope analysis, which makes the nanosystem a promising candidate for further biological study and clinical applications.
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高影响因子
JOURNAL OF COORDINATION CHEMISTRY
·
2019
·
IF 1.685
Xuexue Xu,Shuang Wang,Yaxuan Mi,Huaqian Zhao,Zebao Zheng,Xiaolong Zhao
A polypyridyl ruthenium(II) complex with hydroxyquinoline-derived ligand has been synthesized and characterized. The ability to act as telomeric quadruplex inducer and stabilizer, and quadruplex-binding properties of the complex have been evaluated by absorption and emission analyses, fluorescent intercalator displacement (FID) titrations, circular dichroism (CD) spectroscopy, polymerase chain reaction (PCR) stop assay, color reaction studies, fluorescence resonance energy transfer (FRET) melting assay, Job plot, and molecular modeling. Observations revealed that the complex could well induce and stabilize the formation of antiparallel G-quadruplex of telomeric DNA in the presence or absence of metal cations, and showed superior G-quadruplex selectivity over duplex DNA with remarkable ΔTm value of 18.0 °C even at 50-fold excessive supplies of calf thymus (ct) DNA. The complex exhibited high interaction affinity of 2.56 × 106 M−1 with G-quadruplex DNA and evident luminescence enhancements of 3.1 and 4.2 times for quadruplex binding in Na+ and K+ buffer, respectively. In addition, the 1:1 [quadruplex]/[complex] binding mode ratio was determined. The results suggest that the complex can be developed as potential anticancer reagent through binding and stabilization of G-quadruplex DNA.
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高影响因子
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