NUCLEIC ACIDS RESEARCH
·
2020
·Vol. 48
·期 17
·9986-9994
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IF 11.502
Sun Yuhuan,Zhao Chuanqi,Cui Tingting,Qin Hongshuang,Niu Jingsheng,Ren Jinsong,Qu Xiaogang
Telomeric DNA, whose length homeostasis is closely correlated with immortality of cancer cells, is regarded as a molecular clock for cellular lifespan. Regarding the capacity in forming G-quadruplex, G-rich 3′-overhang (G-overhang) has been considered as an attractive anticancer target. However, it is still challenging to precisely target telomeric G-overhang with current ligands because of the polymorphism of G-quadruplexes in cells. Herein, we construct a telomeric G-overhang-specific near-infrared-traceable DNA nano-hydrolase, which is composed of four parts: (i) dexamethasone for targeting cell nuclei; (ii) complementary DNA for hybridizing with G-overhang; (iii) multinuclear Ce(IV) complexes for hydrolyzing G-overhang; and (iv) upconversion nanoparticles for real-time tracking. The multivalent targeted DNA nano-hydrolase can be traced to precisely digest telomeric G-overhang, which contributes to telomeric DNA shortening and thereby causes cell aging and apoptosis. The anticancer treatment is further proved by in vivo studies. In this way, this design provides a telomeric G-overhang-specific eradication strategy based on a non-G-quadruplex targeting manner.
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高影响因子
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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Acta Biomaterialia
·
2020
·
IF 7.242
Yihang Wu,Ling Wang,Yue Xiong,Quanming Zhou,Linxian Li,Guanyu Chen,Yulei Ping,Gary Davidson,Pavel A. Levkin,Liqian Gao,Wenbin Deng
Development of non-viral gene vectors which can efficiently and safely transfect plasmid DNA and siRNA into cells is of great importance for gene therapy. Despite lots of efforts spent, it is still imperative to develop suitable gene vectors with better transfection efficiency and low cytotoxicity. To this end, we successfully designed, synthesized and screened a library of 120 polymers ( via nucleophilic substitution reaction between dihalides and amines). With cell-based transfection screening assays, 120 polymers were tested to evaluate their transfection efficiency of transporting DNA and siRNA into cells. Our results indicated that hydrophobic modification could greatly enhance cationic polymers’ transfection efficiency, and polymers with long linkers usually showed better transfection performance, especially for polymers with the linker of 1, 12-dibromododecane (L3 linker). Besides, polyalkylamines exhibited better transfection efficiency with the polymer particle size around 200 nm and the zeta potential in the range of + 40 mV to +50 mV. Interestingly, polymer particles made from N15HL3 not only exhibited better DNA transfection efficiency in HEK 293T cells but also showed higher siRNA transfection efficiency in U87 Luc-GFP cells together with low cell toxicity than Lipofectamine 2000 (one of commercial transfection reagents). Therefore, it is hoped that our study here not only provides promising gene vector candidates for further evaluation in gene therapy, but also provides valuable insights for better understanding of the relationship between the chemical structures and gene transfection efficiency to rationally design better non-viral gene vectors for gene therapy in the future.
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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
TRANSITION METAL CHEMISTRY
·
2020
·Vol. 45
·期 7
·493-500
·
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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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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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
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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POLYMER
·
2022
·
IF 4.432
Cheng Deng,Hai Yang,Simin Liu,Zhiyong Zhao
Nanomaterials self-assembled by DNA amphiphiles have great potential application in catalysis, bioimaging and biomedicine. Here, we constructed two kinds of DNA-dendrimer amphiphiles including the G-quadruplex-dendrimer hybrid (G20-Den) and single-stranded DNA-dendrimer hybrid (D20-Den) as a control. Both of them self-assembled into nanofibers with a length of several micrometers in MES buffer, and the diameter of G20-Den nanofibers was smaller than that of D20-Den nanofibers due to the compact stacking of G-quadruplex formed in G20-Den hybrids. At the same time, the catalytic properties of G20-Den nanofiber/hemin, as horseradish peroxidase-mimicking DNAzymes, were investigated. Our results showed that G20-Den nanofiber/hemin, as well as the single-stranded G20/hemin system, exhibited higher catalytic peroxidation activity than D20-Den nanofiber/hemin. Furthermore, through simple ultrafiltration, the recycle of these nanofibers can be simply achieved. This research has provided a new solution for the construction of functional DNA nanomaterials.
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2015
·
IF 3.447
Le-Mao Yu,Xiao-Ru Zhang,Xiao-Bing Li,Yuan Yang,Hong-Yu Wei,Xi-Xin He,Lian-Quan Gu,Zhi-Shu Huang,Yves Pommier,Lin-Kun An
In our previous work, indolizinoquinolinedione derivative 1 was identified as a Top1 catalytic inhibitor. Herein, a series of 6-substituted indolizinoquinolinedione derivatives were synthesized through modification of the parent compound 1 . Top1 cleavage and relaxation assays indicate that none of these novel compounds act as classical Top1 poison, and that the compounds with alkylamino terminus at C-6 side chain, including 8 , 11 – 16 , 18 – 21 , 25 , 26 and 28 – 30 , are the most potent Top1 catalytic inhibitors. Top1-mediated unwinding assay demonstrated that 14 , 22 and 26 were Top1 catalytic inhibitors without Top1-mediated unwinding effect. Moreover, MTT results showed that compounds 26 , 28 – 30 exhibit significant cytotoxicity against human leukemia HL-60 cells, and that compound 26 exerts potent cytotoxicity against A549 lung cancer cells at nanomolar range.
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2019
·
IF 4.833
Wen-Lin Tang,Yu Zhang,De-Xuan Hu,Hui Yang,Qian Yu,Jian-Wen Chen,Keli Agama,Yves Pommier,Lin-Kun An
DNA topoisomerase IB (TOP1) regulates DNA topological structure in many cellular metabolic processes and is a validated target for development of antitumor agents. Our previous study revealed that the benzophenanthridone scaffold is a novel chemotype for the discovery of TOP1 inhibitors. In this work, a series of novel 5-aminoethyl substituted benzophenanthridone derivatives have been synthesized and evaluated for TOP1 inhibition and cytotoxicity. Compound 12 exhibits the most potent TOP1 inhibition (+++) and cytotoxicity in human cancer cell lines with GI 50 values at nanomolar concentration range. 12 induces the cellular TOP1cc formation and DNA damage, resulting in HCT116 cell apoptosis . The pharmacokinetics , acute toxicity and antitumor efficiency in vivo of 12 were also studied.
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高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2023
·
IF 8.4
Ying Li,Pengyue Song,Qingbin Xu,Wenjuan Wu,Nan Long,Jiabo Wang,Lidong Zhou,Ruile Pan,Weijun Kong
An electrochemiluminescence (ECL) aptasensor with aptamer as recognition element, N-doped carbon dots (N-CDs) as luminophore, and DNA tetrahedral nanostructure (DTN) as carrier to loading abundant N-CDs for signal amplification was developed for ultra-sensitive aflatoxin B 1 (AFB 1 ) detection. The complementary DNA (cDNA) was firstly immobilized on the Au electrode (AuE) surface to hybridize with the AFB 1 aptamer. In the presence of AFB 1 , it would competitively with cDNA for binding the aptamer, causing the exposure of cDNA. DTN modified with AFB 1 aptamer on top and N-CDs on the four vertices would combine with cDNA onto the AuE surface to generate ECL signals due to electron transfer between co-reactants (K 2 S 2 O 8 ) and N-CDs, which was positively related to the concentration of AFB 1 . Due to the high specificity of aptamer, the outstanding ECL performance of N-CDs and the enhanced signal output of DTN/N-CDs probes, the as-constructed ECL aptasensor realized excellent sensitivity with a low detection limit of 77 pg/mL and a wide linear concentration of 1.0 × 10 −1 -1.0 × 10 4 ng/mL for AFB 1 , as well as fascinating accuracy with acceptable recoveries of 89.54–111.0% in the spiked Coix seed matrices. Successful application for AFB 1 detection in actual samples confirmed the extensive practicability of the ECL aptasensor, providing a universal platform for more trace contaminants by altering the corresponding aptamers.
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