Pharmaceutics
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2021
·Vol. 13
·期 10
·1582
·
IF 6.321
Zhengqing Yu,Yujia Lu,Wandi Cao,Muhammad Tahir Aleem,Junlong Liu,Jianxun Luo,Ruofeng Yan,Lixin Xu,Xiaokai Song,Xiangrui Li
The pathogen of toxoplasmosis,Toxoplasma gondii(T. gondii), is a zoonotic protozoon that can affect the health of warm-blooded animals including humans. Up to now, an effective vaccine with completely protection is still inaccessible. In this study, the DNA vaccine encodingT. gondiihistone deacetylase SIR2 (pVAX1-SIR2) was constructed. To enhance the efficacy, chitosan and poly (d,l-lactic-co-glycolic)-acid (PLGA) were employed to design nanospheres loaded with the DNA vaccine, denoted as pVAX1-SIR2/CS and pVAX1-SIR2/PLGA nanospheres. The pVAX1-SIR2 plasmids were transfected into HEK 293-T cells, and the expression was evaluated by a laser scanning confocal microscopy. Then, the immune protections of pVAX1-SIR2 plasmid, pVAX1-SIR2/CS nanospheres, and pVAX1-SIR2/PLGA nanospheres were evaluated in a laboratory animal model. The in vivo findings indicated that pVAX1-SIR2/CS and pVAX1-SIR2/PLGA nanospheres could generate a mixed Th1/Th2 immune response, as indicated by the regulated production of antibodies and cytokines, the enhanced maturation and major histocompatibility complex (MHC) expression of dendritic cells (DCs), the induced splenocyte proliferation, and the increased percentages of CD4+and CD8+T lymphocytes. Furthermore, this enhanced immunity could obviously reduce the parasite burden in immunized animals through a lethal dose ofT. gondiiRH strain challenge. All these results propose that pVAX1-SIR2 plasmids entrapped in chitosan or PLGA nanospheres could be the promising vaccines against acuteT. gondiiinfections and deserve further investigations.Keywords:Toxoplasma gondii;histone deacetylase;SIR2;chitosan;PLGA;immune protection
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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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JOURNAL OF NANOPARTICLE RESEARCH
·
2021
·Vol. 24
·期 1
·1-12
·
IF 2.253
Gong Zhenhu,Wei Zongnan,Liu Yizhang,Xiao Lufei
A ratiometric fluorescent deoxyribonucleic acid (DNA) probe was synthesized using the photoinduced electron transfer (PET) mechanism, involving the interactions between different fluorescent components and electron acceptors. Double-emission carboxyl-functionalized semiconducting polymer dots with an average diameter of 26.7 nm were synthesized using the nanoprecipitation method and applied as a fluorophore, and methylene blue (MB) was used as the electron acceptor. PET between different polymer dots components and MB can achieve ratiometric modulation of the overall fluorescence in the system. The addition of DNA restores the fluorescence intensity, because the strong interactions between DNA and MB result in MB being separated from the polymer dots. Under optimized experimental conditions, system fluorescence was restored to its maximum when the concentration of DNA reached 200 nM; the linear range was 0.006–200 nM ( R 2 = 0.995). This probe was reasonably free from interference, showing a good response to DNA, with strong application data from actual samples.
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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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BIOSENSORS & BIOELECTRONICS
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2021
·
IF 10.618
M.R. Ali,M.S. Bacchu,M.A.A. Setu,S. Akter,M.N. Hasan,F.T. Chowdhury,M.M. Rahman,M.S. Ahommed,M.Z.H. Khan
Due to the epidemics of emerging microbial diseases worldwide, the accurate and rapid quantification of pathogenic bacteria is extremely critical. In this work, a highly sensitive DNA-based electrochemical biosensor has been developed to detect Vibrio cholerae using gold nanocube and 3-aminopropyltriethoxysilane (APTES) modified glassy carbon electrode (GCE) with DNA carrier matrix. Electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM) experiments were performed to interrogate the proposed sensor at each stage of preparation. The biosensor has demonstrated high sensitivity with a wide linear response range to target DNA from 10 −8 to 10 −14 ( R 2 = 0.992 ) and 10 −14 to 10 −27 molL −1 ( R 2 = 0.993 ) with a limit of detection (LOD) value of 7.41 × 10 −30 molL −1 ( S/N = 5 ). The biosensor also exhibits a selective detection behavior in bacterial cultures that belong to the same and distant genera. Moreover, the proposed sensor can be used for six consecutive DNA assays with a repeatability relative standard deviations (RSD) value of 5% ( n = 5). Besides, the DNA biosensor shows excellent recovery for detecting V. cholerae in poultry feces, indicating that the designed biosensor could become a powerful tool for pathogenic microorganisms screening in clinical diagnostics, food safety, and environmental monitoring.
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ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Yiting Jiang,Minxuan Sun,Nan Ouyang,Yuguo Tang,Peng Miao
Herein, we develop a novel and effective combination nanoplatform for cancer theranostics. Folic acid (FA) is first modified on the photothermal agent of polydopamine (PDA), which possesses excellent near-infrared (NIR) absorbance and thermal conversion features. Temperature-sensitive silver nanoclusters (AgNCs) are then synthesized on the DNA template that also loads the anticancer drug doxorubicin (Dox). After accumulation in cancer cells, PDA generates cytotoxic heat upon excitation of NIR light for photothermal therapy. On the other hand, the temperature increment is able to destroy the template of AgNCs, leading to the fluorescence variation and controlled release of Dox for chemotherapy. The combined nanosystem exhibits outstanding fluorescence tracing, NIR photothermal transduction, as well as chemo drug delivery capabilities. Both in vitro and in vivo results demonstrate excellent tumor growth suppression phenomena and no apparent adverse effects. This research provides a powerful targeted nanoplatform for cancer theranostics, which may have great potential value for future clinical applications.
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NEW JOURNAL OF CHEMISTRY
·
2020
·Vol. 44
·期 40
·17296-17301
·
IF 3.288
Tao Lei,Ting Huang,Tianze Wang,Peng Yu,Taiping Qing,Beixi Nie
Thiocyanate (SCN−) is a metabolite of cyanide detoxification, which is considered to be a biomarker of environmental tobacco smoke exposure. Herein, a simple, fast and label-free fluorescent sensor was developed to determine SCN− based on the in situ formation of DNA-templated fluorescent copper nanoclusters (CuNCs). Without SCN−, the Cu(II) ions in buffer were reduced by ascorbic acid and then accumulated on the DNA template, showing a high fluorescence. However, in the presence of SCN−, the Cu(II) ions reacted with thiocyanate and then the remaining unreacted Cu(II) ions were reduced by ascorbic acid, producing a small amount of the CuNCs and a weak fluorescence. Several important parameters such as the concentrations of DNA, Cu(II) ions and ascorbic acid were optimized. Under the optimized conditions, the linear range was 10–100 μM and the limit of detection (LOD) was 4.94 μM for thiocyanate assay. Due to the strong chelation between SCN− and the Cu(II) ions, high selectivity was achieved for SCN− detection by this sensor, with practical applications in real water and artificial saliva. The operation process is simple and the signal response of this method to thiocyanate is fast, within a few minutes. Therefore, the developed assay has great potential to determine thiocyanate for the assessment of water safety and human health.
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Acta Biomaterialia
·
2020
·
IF 7.242
Hongmei Geng,Ze Yin,Chunyang Zhou,Chunlei Guo
Over the past few decades, DNA-based computing technology has become a rapidly developing technology and shown remarkable capabilities in handling complex computational problems. However, most of the logical operations that DNA computer can achieve are still very basic or using large-scale operations to realize complex functions, especially in mathematics. Graphene oxide (GO) is an ideal nanomaterial for biological computing, which has been used in our previous work to perform basic logic operations. Here, we utilize GO to implement far more complex and large-scale logical computing. For the first time, in this work, we utilize the unique interaction between GO and a variety of classified single-stranded DNAs as the reaction platform, by segmenting and encoding the DNA sequences , and programming the interactions between inputs and between the inputs and reaction platform, two relative large-scale logic operations, 6-bit square-root and 9-bit cube-root logical circuits are realized. This study provides a simple but efficient method for advanced and large-scale logical mathematic operations in biotechnology, opening a new horizon for building biocomputer-based innovative functional devices.
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CHINESE CHEMICAL LETTERS
·
2021
·
IF 6.779
Yuan Liu,Gaojian Yang,Taotao Li,Yan Deng,Zhu Chen,Nongyue He
An improved ssDNA library immobilized systematic evolution of ligands by enrichment (SELEX) was applied to select aptamers against carbaryl. After nine selection rounds, a highly enriched ssDNA pool was obtained. The Apta3 was demonstrated as the optimal aptamer. In order to facilitate the modification of aptamer, the Apta3 was further truncated with the dissociation constant ( K d ) of 0.364 ± 0.055 μmol/L and a fluorescent aptasensor was developed. The linear range for carbaryl was from 100 nmol/L to 1500 nmol/L, with the limit of detection was as low as 15.23 nmol/L. Besides, the biosensor was validated for the carbaryl spiked real samples, and the recoveries were between 97.7% and 107.3%.
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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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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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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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