JOURNAL OF MOLECULAR LIQUIDS
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2021
·
IF 6.165
Danfeng Wang,Min Liu,Yushu Wu,Yanna Zhao,Qingpeng Wang,Tianxin Weng,Lu Wang,He Liu,Yongfang Ren,Jun Han
Self-assembled DNA nanostructures, as a novel type of nano-biomaterials, are widely used for smart and targeted drug delivery due to their precise structures and versatile functions. The binding affinity of drugs to DNA nanostructures plays an important role in drug loading, release and efficacy. The interaction of mithramycin (MTR) with AS1411-tethered DNA nanotrains (AS1411NTrs) in the presence of different divalent metal ions (Mg 2+ , Zn 2+ , and Mn 2+ ) was studied by fluorescence spectroscopy, differential scanning calorimetry and viscosity measurement. The binding mode between the MTR dimers and AS1411NTrs was determined by viscosity experiment and melting temperature measurement. The thermodynamic parameters of the binding process (binding stoichiometry, binding constant, enthalpy change, entropy change and Gibbs free energy change) were determined by fluorescence spectroscopy and differential scanning calorimetry, and the effect of different metal ions on the binding was compared. The release of the MTR dimers loaded by AS1411NTrs in the absence and presence of DNase I was analyzed. The in vitro cytotoxicity of the MTR dimers to HepG2 cancer cells and L02 normal cells and their intracellular uptake efficiency were evaluated. The binding parameters were correlated with the loading, release and cytotoxicity of the MTR dimers. These studies showed that AS1411NTrs had high drug loading and sustained release effect on (MTR) 2 Mg 2+ , (MTR) 2 Zn 2+ and (MTR) 2 Mn 2+ . This drug loading system improved the lethality to cancer cells and reduced the side effects on normal cells. This study may provide a theoretical basis for the clinical application of MTR loaded by DNA nanostructures.
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BIOORGANIC CHEMISTRY
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2021
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IF 5.275
Jin-Yu Liu,Xu-Ying Liu,Rui Liu,Fang Tang,Jing-Bo Yang,Quan Tang,Zhong-Lin Lu,Hai-Jun Qiao,Lan He
Two-photon fluorescent Acenaphtho[1,2- b ]quinoxaline (ANQ) and the hydrophilic di-(triazole-[12]aneN 3 ) moieties were combined through an alkyl chain ( ANQ-A-M ) or a β -hairpin motif with two aromatic γ -amino acid residues ( ANQ-H-M ) to explore their capabilities for in vitro and in vivo gene delivery and tracing. ANQ-A-M and ANQ-H-M showed the same maximum absorption at 420 nm, and their fluorescent intensities around 650 nm were varied in different solvents and became poor in the protic solvents. Gel electrophoresis assays indicated that both compounds completely retarded the migration of pDNA at 20 μM in the presence of DOPE . However, the DNA condensation with ANQ-H-M was not reversible, and the particle size of the corresponding complexes were larger indicated from the SEM and DLS measurements. In vitro transfections indicated ANQ-A-M /DOPE achieved Luciferase and GFP expressions were to be 7.9- and 5.7-fold of those by Lipo2000 in A549 cells respectively. However, ANQ-H-M showed very poor transfection efficiency in Luciferase expression. With the help of single/two-photon fluorescence imaging it clearly demonstrated that the successful transfection of ANQ-A-M was attributed to its cellular uptake, apparent lysosomal escape, and reversible release of DNA; and the poor transfection of ANQ-H-M was resulted from the aggregation of the DNA complexes which prevented them from the cellular uptake, and also the strong binding ability which is not easy to release DNA. ANQ-A-M /DOPE also exhibited robust gene silencing (83% knockdown of Luciferase) and GFP expression (2.47-fold higher) efficiency compared with Lipo2000 in A549 and zebrafish, respectively. The work demonstrated that the linkage structure between fluorescent and di(triazole-[12]aneN 3 ) played the important role for their gene delivery performance, and that ANQ-A-M represents a vector with the strong transfection efficiency in vitro and in vivo as well as the efficient real time bioimaging properties, which is potential for the development in biomedical research.
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SENSORS AND ACTUATORS B-CHEMICAL
·
2020
·
IF 7.1
Junyang Chen,Mengke Wang,Xiaobin Zhou,Yixin Nie,Xingguang Su
Specific and sensitive detection of target DNA plays a significant role in clinical diagnosis and biomedical research. Herein, a sensitive ratio fluorescence biosensor was constructed based on in-situ generation of fluorescent copper nanoclusters (CuNCs) on the DNA modified graphene quantum dots (GQDs) for the detection of HTLV-I DNA. Firstly, large amount of AT rich single DNA (o-DNA) can be released from the designed hairpin DNA in the presence of trace target DNA via exonuclease III assisted target recycling amplification strategy. Then, the released o-DNA hybridized with the complementary DNA1 which was modified on the surface of GQDs, and the formed hybridized DNA with blunt 3′-hydroxylated terminus that couldn’t be digested by exonuclease I could act as the template for the generation of fluorescent CuNCs. While in the absence of target DNA, the o-DNA couldn’t be released, thus the DNA1 with 3′overhang ends could be degraded by exonuclease I, which resulted in the in-situ generation of fluorescent CuNCs on the surface of GQDs was blocked owing to the lack of DNA template. The GQD fluorescence in the GQD-CuNC nanohybrid was almost uninfluenced during the whole process. Therefore, with the GQD serving as the reference and CuNC acting as the reporter signal, there was an excellent linear relationship between the change of fluorescence intensity ratio (F 595 /F 445 ) and the concentration of HTLV-I DNA in the range of 20 pM-12 nM with a detection limit of 10 pM. Furthermore, the biosensor exhibited satisfactory results for monitoring the presence of HTLV-I DNA in human serum.
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Scientific Reports
·
2020
·Vol. 10
·期 1
·1-14
·
IF 3.998
Zhang Chao,Zhang Fanghua,Han Mengnan,Wang Xuming,Du Jie,Zhang Honglei,Li Wei
Combination chemotherapy is still of great importance as part of the standard clinical care for patients with HER2 positive breast cancer. As an attractive component, gold nanoparticles (AuNPs) have been extensively studied as biosafety nanomaterials, but they are rarely explored as drug nanocarriers for targeted co-delivery of multiple chemotherapeutics. Herein, a novel affibody-DNA hybrid strands modified AuNPs were fabricated for co-loading nucleoside analogue (5-fluorodeoxyuridine, FUdR) and anthracycline (doxorubicin, Dox). FUdRs were integrated into DNA hybrid strands decorated on AuNPs by DNA solid phase synthesis, and Dox molecules were intercalated into their duplex regions. Affibody molecules coupled to the DNA hybrid strands were distributed the surface of AuNPs, giving them targeting for HER2. The new dual-drug-containing affibody-DNA-AuNPs (Dox@affi-F/AuNPs) owned compact and stable spherical nanostructures, and precise drug loading. Cytotoxicity tests demonstrated that these nanoparticles caused a higher inhibition in HER2 overexpressing breast cancer cells, and showed better synergistic antitumor activity than simple mixture of the two drugs. The related mechanistic studies proved that Dox@affi-F/AuNPs achieved a remarkable combined antitumor activity of Dox and FUdR by promoting more cells to enter apoptosis pathway. Our work provided a nanomedicine platform for targeted co-delivery of nucleoside analog therapeutics and anthracycline anticancer drugs to achieve synergistic treatment of HER2 + cancer.
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SENSORS AND ACTUATORS B-CHEMICAL
·
2020
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IF 7.1
Hui Liu,Jinshui Wang,Huali Jin,Min Wei,Wenjie Ren,Yurong Zhang,Ligen Wu,Baoshan He
A sensitive electrochemical biosensor was constructed for Hg 2+ detection based on peonylike Cu-MOFs in situ growth of PtPd NPs bimetallic label S 1 and Mg 2+ -dependent DNAzyme-driven DNA Walker dual amplification signal strategy. The hairpin DNA (HP) and signal label [email protected] NPs/S 1 were first used to self-assemble on the gold nanorods/poly (diallyldimethylammonium chloride) functionalized graphene (AuNRs/PDDA-Gr) modified electrode, at this time, Cu ions can undergo a valence change to produce a larger initial signal. Here, we designed S 2 that can perform dual functions and contains two sequences, on was a substrate sequence of the Mg 2+ -dependent DNAzyme and the other was a sequence complementary to HP. In the presence of target Hg 2+ , HP was opened and hybridized with enzymatically sequenced DNA Walker (S 2 ) to preferentially form thymine-Hg 2+ -thymine (T-Hg 2+ -T). Then, DNA Walker exhibited catalytic activity of DNAzyme in the presence of Mg 2+ to continuously cleave [email protected] NPs/S 1 , resulting in a decrease of electrochemical signal. Under optimal conditions, the change of current was linearly related to the negative logarithm of the Hg 2+ concentration in the detection range of 0.001–100 nM with a low detection limit of 0.52 pM. Moreover, the proposed aptasensor was successfully applied in detection of milk powder samples.
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MICROCHIMICA ACTA
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2020
·Vol. 187
·期 2
·1-7
·
IF 6.232
Wei Min,Xin Lingkun,Feng Shuo,Liu Yong
A complementary DNA (cDNA) was designed to simultaneously hybridize with the ochratoxin A (OTA) aptamer and the fumonisin B1 (FB1) aptamer to form a unique Y-shaped DNA structure and to achieve simultaneous detection. Gold nanorods (AuNRs) were used to immobilize thionine (Th), thiolated ferrocene (Fc), thiolated OTA aptamer (Apt1), and thiolated FB1 aptamer (Apt2), to form an amplified signal element and a recognition element. The Apt1-AuNRs-Th complex and the Apt2-AuNRs-Fc complex hybridize with cDNA to form a unique Y-DNA structure on a gold electrode. This produces two initial electrochemical signals [with 177 μΑ cm −2 near −0.2 V, and 3121 μΑ cm −2 near +0.46 V (vs. Ag/AgCl)] by differential pulse voltammetry. Upon addition of 0.1 ng mL −1 OTA and 0.1 ng mL −1 FB1, the aptamers bind the two toxins. This results in the release of Apt1-AuNRs-Th and Apt2-AuNRs-Fc, so the peak currents densities decrease to 115 μΑ cm −2 and 209 μΑ cm −2 . The assay allows simultaneous determination of OTA and FB1 in the 1.0 pg·mL −1 to 100 ng·mL −1 concentration ranges, with LODs of 0.47 and 0.26 pg·mL −1 . The assay is reproducible, stable and specific. It was applied to the determination of OTA and FB1 in spiked beer, with recoveries between 89.0% and 102.0%.
Schematic representation of OTA and FB 1 detection based on Apt 2 -AuNRs-Fc/Apt 1 -AuNRs-Th/cDNA/AuE. (AuNRs: Gold nanorods; Th: thionine; Fc: ferrocene; SH: thiol; BSA: Bovine serum albumin; cDNA: Complementary DNA; Apt 1 : Aptamer1; Apt 2 : Aptamer2; OTA: Ochratoxin A; FB 1 : Fumonisin B 1 ).
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ANALYTICA CHIMICA ACTA
·
2017
·
IF 4.95
Meng Chen,Ning Gan,Tianhua Li,Ye Wang,Qing Xu,Yinji Chen
An effective electrochemical aptasensor has been developed for the detection of multiplex antibiotics using Y-shaped DNA probes . These probes-based metal ions encoded the nanoscale metal-organic frameworks (NMOF) as a substrate, and circular strand-replacement DNA polymerization (CSRP) target triggered the amplification strategy. The Y-DNA probes (Y-DNA) were assembled using an assisted DNA probe (assisted DNA labeled with magnetic gold nanoparticles) which can hybridize to the captured DNA probe (consisting of aptamer and primer recognition region), and signal tags (NMOF encapsulating signal DNAs and different metal ions such as Pb 2+ or Cd 2+ ). Notably, NMOF was employed as the developed platform with a large specific area to load abundant metal ions that can produce distinguishable signals. In the presence of targets, chloramphenicol (CAP) and oxytetracycline (OTC) as models, the conformational change of the captured DNA can disassemble the Y-DNA probes that can consequently release the signal tags in the supernatant due to the high affinity of targets towards the aptamer domain than its complementary sequences. Subsequently, the exposed sequences of captured DNA serve as the initiators for triggering the target cyclic-induced polymerization with the assistance of Bst DNA polymerase. Thus, numerous signal tags could be detected by square wave voltammetry in the supernatant after magnetic separation, thereby amplifying the electrochemical signals. The proposed strategy exhibited a high sensitivity to antibiotics with a detection limit of 33 and 48 fM (S/N = 3) towards CAP and OTC, respectively. Moreover, this aptasensor showed promising applications for the detection of other analytes.
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TALANTA
·
2023
·
IF 6.1
Hongqin Yang,Lian Xia,Jia Zheng,Zhengmin Xie,Jianli Zhou,Yuangen Wu
Clothianidin pesticide not only pollutes the ecological environment, but also poses a potential threat to human health. Thus, it is of great importance to develop efficient and accurate methods to recognize and detect clothianidin residues in agricultural products. Aptamer has the advantages of easy modification, high affinity and good stability, which is particularly suitable as a recognition biomolecule for pesticide detection. However, the aptamer against clothianidin has not been reported. Herein, the aptamer (named CLO-1) had good selectivity and strong affinity ( K d = 40.66 ± 3.47 nM) to clothianidin pesticide, which was screened for the first time by Capture-SELEX strategy. The binding effect of CLO-1 aptamer to clothianidin was further studied by circular dichroism (CD) spectroscopy and molecular docking technique. Finally, the CLO-1 aptamer was used as the recognition molecule to construct a label-free fluorescent aptasensor using GeneGreen dye as sensing signal for the highly sensitive detection of clothianidin pesticide. The constructed fluorescent aptasensor had the limit of detection (LOD) as low as 5.527 μg L −1 for clothianidin, and displayed good selectivity against other competitive pesticides. The aptasensor was applied to detect the clothianidin spiked in tomatoes, pears and cabbages, and the recovery rate was good in the range of 81.99%–106.64%. This study provides a good application prospect for the recognition and detection of clothianidin.
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JOURNAL OF HAZARDOUS MATERIALS
·
2023
·
IF 13.6
Yanli Zhang,Yulin Zhang,Ye Lei,Junrong Wu,Yiyuan Kang,Shuo Zheng,Longquan Shao
During pregnancy, the human body is quite vulnerable to external stimuli. Zinc oxide nanoparticles (ZnO-NPs) are widely used in daily life, and they enter the human body via environmental or biomedical exposure, thus having potential risks. Although accumulating studies have demonstrated the toxic effects of ZnO-NPs, few studies have addressed the effect of prenatal ZnO-NP exposure on fetal brain tissue development. Here, we systematically studied ZnO-NP-induced fetal brain damage and the underlying mechanism. Using in vivo and in vitro assays, we found that ZnO-NPs could cross the underdeveloped blood brain barrier and enter fetal brain tissue, where they could be endocytosed by microglia. ZnO-NP exposure impaired mitochondrial function and induced autophagosome overaccumulation by downregulation of Mic60, thus inducing microglial inflammation. Mechanistically, ZnO-NPs increased Mic60 ubiquitination by activating MDM2, resulting in imbalanced mitochondrial homeostasis. Inhibition of Mic60 ubiquitination by MDM2 silencing significantly attenuated the mitochondrial damage induced by ZnO-NPs, thereby preventing autophagosome overaccumulation and reducing ZnO-NP-mediated inflammation and neuronal DNA damage. Our results demonstrate that ZnO-NPs are likely to disrupt mitochondrial homeostasis, inducing abnormal autophagic flux and microglial inflammation and secondary neuronal damage in the fetus. We hope the information provided in our study will improve the understanding of the effects of prenatal ZnO-NP exposure on fetal brain tissue development and draw more attention to the daily use of and therapeutic exposure to ZnO-NPs among pregnant women.
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MOLECULES
·
2023
·Vol. 28
·期 5
·2149
·
IF 4.6
Zhe Chen,Zhuoyi Wang,Yihua Yuan,Bo Liu,Jiangbo Yu,Zhiwen Wei,Keming Yun
DNA self-assembled fluorescent nanoprobes have been developed for bio-imaging owing to their high resistance to enzyme degradation and great cellular uptake capacity. In this work, we designed a new Y-shaped DNA fluorescent nanoprobe (YFNP) with aggregation-induced emission (AIE) characteristic for microRNA imaging in living cells. With the modification of the AIE dye, the constructed YFNP had a relatively low background fluorescence. However, the YFNP could emit a strong fluorescence due to the generation of microRNA-triggered AIE effect in the presence of target microRNA. Based on the proposed target-triggered emission enhancement strategy, microRNA-21 was detected sensitively and specifically with a detection limit of 122.8 pM. The designed YFNP showed higher bio-stability and cell uptake than the single-stranded DNA fluorescent probe, which has been successfully applied for microRNA imaging in living cells. More importantly, the microRNA-triggered dendrimer structure could be formed after the recognition of target microRNA, achieving a reliable microRNA imaging with a high spatiotemporal resolution. We expect that the proposed YFNP will become a promising candidate for bio-sensing and bio-imaging.Keywords:DNA fluorescent nanoprobes;Y-shaped;aggregation-induced emission;microRNA;live-cell imaging
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ANALYTICAL CHEMISTRY
·
2019
·
IF 6.35
Yue Lin,Jinpeng Jia,Rui Yang,Daozhen Chen,Jian Wang,Fang Luo,Longhua Guo,Bin Qiu,Zhenyu Lin
DNA tetrahedron nanostructure (DTNs) has the merits of simple synthesis, high yield, structural stability, and mechanical rigidity, and its three-dimensional structure provides a satisfactory biosensing interface to the improvement of the binding efficiency of antigenic proteins and antibodies. Electrochemiluminescence (ECL) reagent, tris(4,4′-dicarboxylicacid-2,2′-bipyridyl)ruthenium(II) dichloride (Ru(dcbpy)3Cl2), was modified on the electrode through the formation of classical sandwich complex of antibody–antigen–antibody. ECL response of the system increased with the increment of the target (golgi protein 73 (GP73) in this study) with high selectivity. Besides, the composed double-stranded DNA (dsDNA) in each side of DTNs could act as an excellent carrier of methylene blue (MB), thus producing a stable electrochemical internal reference signal on the electrode surface to correct the potential interferences. Therefore, a highly selective and reproductive ratiometric immunosensor was developed on the basis of the ratio of ECL of Ru(dcbpy)3Cl2 and electrochemistry of MB. The ratio value of the ECL/electrochemistry had a linear relationship with GP73 concentration in the range of 15 pg/mL–0.7 ng/mL, and the limit of detection was 15 pg/mL. The proposed ratiometric ECL immunoassay has been applied to detect GP73 in real serum samples with satisfactory results.
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TALANTA
·
2019
·
IF 4.916
Guangyang Xiao,Beibei Chen,Man He,Xiaoting Li,Bin Hu
In this work, a simple, sensitive and specific assay for DNA was proposed by combining inductively coupled plasma mass spectrometry (ICP-MS) detection with gold nanoparticle (AuNPs) amplification and isothermal circular strand-displacement polymerization reaction (ICSDPR). First, AuNPs were decorated with hairpin-structured DNA (HP-DNA) through Au–S bond to form the AuNPs probe. The ICSDPR was conducted on AuNPs probe in a homogeneous phase to realize the dual amplification and simplify the analytical process at the same time. By using a biotin modified primer, AuNPs were connected with biotins after the ICSDPR, then captured by the streptavidin modified magnetic beads (SA-MBs), and finally detected by ICP-MS. Many key factors including probe volume, hybridization time, polymerase amount, primer concentration, enzyme reaction time, SA-MBs capture time and desorption time were optimized. Under the optimized condition, the proposed method could detect target DNA as low as 45 zmol (8.9 fM in 5 μL) in a relative short time (about 4.5 h) with good specificity, and the linear range of this method is 0.1–10000 pM, the relative standard deviations are in the range of 3.6–6.4%. The proposed method was applied for determination of target DNA in human serum samples, the recovery for the spiked human serum samples is in the range of 84–120%. It demonstrates a good application potential of the developed method for biological studies and clinical diagnosis of human pathogenic diseases.
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