DNA has become a promising material to construct high-order structures and molecular devices owing to its sequence programmability. Herein, a DNA machine based on branched catalytic hairpin assembly ...(bCHA) is introduced for dynamic self-assembly of DNA dendrimers. For this system, a Y-shaped hairpin trimer tethered with three kinds of hairpins (H1, H2 and H3) is constructed. The introduction of an initiator (I) triggers a cascade of CHA reactions among hairpin trimers, leading to the formation of DNA dendrimers. Through labeling fluorophore/quencher pairs in the hairpin trimers, this catalytic DNA machine is applied as a versatile amplification platform to analyze nucleic acids using microRNA-155 (miR-155) as a model analyte. Benefiting from the "diffusion effect", the proposed bCHA achieves a greatly improved sensitivity in comparison with traditional CHA. This catalytic amplifier exhibits high sensitivity toward miR-155 detection with a dynamic range from 2.5 nM to 500 nM and demonstrates excellent selectivity to distinguish the single-base mismatched sequence from the perfectly complementary one, which is further applied to detect low-abundance miR-155 spiked in complex matrices with minimal interference. This method is further applied for
imaging of miR-155 in different live cells. The bCHA reaction can be specifically triggered by intracellular miR-155, achieving monitoring of the dynamic miRNA expression and distribution. Overall, our proposed enzyme-free dynamic DNA self-assembly strategy provides a versatile approach for the development of DNA nanotechnology in biosensing and bioimaging, and monitoring the cellular miRNA-related biological events.
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•DNA-Au nanomachine activated by tumor microenvironment GSH is constructed.•G-quadruplexes are incorporated to target tumor and modulate tumor hypoxia for enhanced PDT.•Triple ...combination of PDT/PTT/chemotherapy is achieved for cancer treatment.
Multimodal therapy is a combination of different therapeutic modalities within one single platform to enhance treatment efficiency, which holds great promise in biomedical research and clinical practice. Herein, a glutathione (GSH)-activated DNA-Au nanomachine with tumor-targeting capacity has been developed for imaging-guided photodynamic/photothermal/chemo combination therapy of murine breast cancer. In this theranostic nanoplatform, G-quadruplex double-stranded DNA (G-dsDNA) containing AS1411 aptamer is served as not only the targeting unit to specifically recognize murine 4T1 breast cancer cells but also the carrier for loading photosensitizer chlorins e6 (Ce6), iron-containing porphyrin hemin and anticancer drug doxorubicin (Dox). In tumor microenvironment, the excessive GSH triggers the rupture of disulfide bridges and results in the dissociation of DNA-Au nanomachine along with the release of Dox for chemotherapy and the aggregation of AuNPs for photothermal therapy (PTT) as well as in situ imaging. Meanwhile, hemin and Ce6 delivered by G-quadruplexes alleviate the tumor hypoxia, which further promotes the generation of reactive oxygen species (ROS) for enhanced photodynamic therapy (PDT). The in vitro and in vivo assays validate that the combination of PDT/PTT/chemotherapy shows a high efficiency for targeted damage of 4T1 cells and inhibition of tumor growth. Therefore, the proposed multifunctional DNA-Au nanomachine provides a powerful and robust theranostic nanoplatform for imaging-guided combinatorial anticancer therapy.
The Raman probe plays an essential role in sensitive surface-enhanced Raman scattering (SERS) assay. Here, a novel Raman probe was developed by assembling gold nanoparticles in triangular pyramid DNA ...(TP-Au NPs). Such probe with intense electromagnetic hot spots can provide dramatically enhanced Raman scattering. Through assembling recognition DNA on one corner of the TP-DNA, the recognition event is definite and designable. The probe was characterized through TEM, and its SERS superiority was investigated. As models, circulating tumor cells and exosomes were detected with high sensitivity and selectivity by using this probe. Meanwhile, the developed SERS probe can also perform well in real world samples.
Multifunctional AgNPs@GQDs with nanozyme activity have been applied for dual-mode biosensing and cancer theranostics based on the H2O2-responsive degradation.
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A multifunctional ...nanocomposite of AgNPs@GQDs is prepared by synergistic in-situ growth of silver nanoparticles (AgNPs) on the complex of tannic acid (TA) and graphene quantum dots (GQDs) for the construction of dual-mode biosensing platform and cancer theranostics. The nanocomposite exhibits a hydrogen peroxide (H2O2)-responsive degradation, in which Ag0 is oxidized to Ag+ along with the release of oxidized TA and GQDs. The degradation induces the decreased absorbance and enhanced fluorescence (FL) intensity due to the suppression of Förster resonance energy transfer (FRET) in AgNPs@GQDs, which is employed for colorimetric/fluorescence dual-mode sensing of H2O2. The intrinsic peroxidase-like activity of GQDs nanozyme can effectively catalyze the oxidation reaction, enhancing the detection sensitivity significantly. Based on the generation of H2O2 from the oxidation of glucose with the catalysis of glucose oxidase (GOx), this nanoprobe is versatilely used for the determination of glucose in human serum. Further, through combining the H2O2-responsive degradation of AgNPs@GQDs with high H2O2 level in cancer cells, the nanocomposites exhibit good performance in cancer cell recognition and therapy, in which the synergistic anticancer effect of Ag+ and oxidized TA contribute to effective cell death, and the liberated GQDs are used to monitor the therapeutic effect by cell imaging.
The analysis of DNA methylation and MTase activities is very important in the early clinical diagnosis of cancer, on purposes of providing insights into the mechanism of gene repression and ...developing novel drugs of treating methylation-related diseases. Combining the dendritic rolling circle amplification and Mg2+-dependent DNAzyme with a function of catalyzing the generation of a fluorophore-labeled nucleic acid acting as readout signal for the analyses, a new fluorescent method for DNA methyltransferase detection was reported. In the presence of DNA methyltransferases (MTase), the methylation-responsive sequence of double-stranded DNA probe was methylated and then cleaved by the methylation-sensitive restriction endonuclease DpnI. The cleaved hybrid DNA probe then functioned as a signal primer to initiate the dendritic rolling circle amplification reaction, containing a circular DNA and a structurally tailored hairpin structure. Subsequently, the circular nucleic acid template produced a complementary sequence to the Mg2+-dependent DNAzyme and a sequence identical to the loop region of the co-added hairpin structure. At last, a fluorescence readout signal was afforded by the DNAzyme-catalyzed cleavage of a fluorophore/quencher-modified substrate. This method enabled the analysis of the target MTase with a detection limit up to 0.36 U mL−1, and a dynamic range was obtained from 1.0 to 10 U mL−1. Moreover, the proposed strategy was successfully applied in real sample assay. With this assay, the inhibitors of MTase were evaluated and screened which might be helpful for the discovery of anticancer drugs.
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•Mg2+-dependent DNAzyme and signal amplification strategy were implemented for the detection of DNA methyltransferase.•The dendritic rolling circle amplification was employed for signal amplified process.•This strategy exhibits an excellent specificity and is successfully applied in evaluation of the inhibitors of MTase.
In this work, isothermal circular strand-displacement polymerization amplification assay is developed for highly specific and sensitive detection of adenosine triphosphate (ATP). The amplification ...process consists of circular common target molecule-displacement polymerization (CCDP) and circular nucleic acid strand-displacement polymerization (CNDP). In the presence of ATP, the complementary strand was released from the aptamer by the target recognition of ATP, and catalyzed the subsequent cycle reaction. With the polymerase and primer, the displaced target triggers the process of CCDP. With the involvement of nicking endonuclease, the released complementary strand triggers the CNDP. Combined CCDP with CNDP, the exponentially produced fluorescence probes are obtained, achieving a detection limit of ATP as low as 2.6×10−10M. Moreover, the proposed strategy exhibits an excellent specificity and is successfully applied in real sample assay which demonstrates potential application in practical samples.
•The method has implemented two kinds of enzymes for sensitive detection of ATP.•The amplification process consists of CCDP and CNDP.•The proposed strategy is successfully applied in real sample assay.
In this work, a simple and novel quartz crystal microbalance (QCM) assay is demonstrated to selectively and sensitively detect the adenosine triphosphate (ATP). The amplification process consists of ...circular nucleic acid strand-displacement polymerization, aptamer recognition strategy and nanoparticle signal amplification. With the involvement of an aptamer-based complex, two amplification reaction templates and AuNP-functionalized probes, the whole circle amplification process is triggered by the target recognition of ATP. As an efficient mass amplifier, AuNP-functionalized probes are introduced to enhance the QCM signals. As a result of DNA multiple amplification, a large number of AuNP-functionalized probes are released and hybridized with the capture probes on the gold electrode. Therefore the QCM signals are significantly enhanced, reaching a detection limit of ATP as low as 1.3 nM. This strategy can be conveniently used for any aptamer-target binding events with other biological detection such as protein and small molecules. Moreover, the practical determination of ATP in cancer cells demonstrates the feasibility of this QCM approach and potential application in clinical diagnostics.
We report a strategy for the transduction of DNA hybridization into a readily detectable photoelectrochemical signal by means of a conformational change analogous to electrochemical DNA (E-DNA) ...approach. To demonstrate the effect of distance change for photosensitizer to the surface of electrode on the change of photocurrent, photosensitizer Ru(bpy)2(dcbpy)2+ tagged DNA stem–loop structures were self-assembled onto a nanogold modified ITO electrode. Hybridization induced a large conformational change in DNA structure, which in turn significantly altered the electron-transfer tunneling distance between the electrode and photosensitizer. The resulting change in photocurrent was proportional to the concentration of DNA in the range of 1.0×10−10–8.0×10−9M. In order to improve the sensitivity of the photoelectrochemical biosensor, an amplified detection method based on isothermal strand displacement polymerization reaction was employed. With multiple rounds of isothermal strand replication, which led to strand displacement and constituted consecutive signal amplification, a detection limit of 9.4×10−14M target DNA was achieved.
► A photoelectrochemical biosensor based on conformational change of DNA was developed. ► Circular strand-displacement polymerization reaction was employed. ► This strategy is simple, selective and sensitive.
Solid‐state polymer electrolytes are an important factor in the deployment of high‐safety and high‐energy‐density solid‐state lithium metal batteries. Nevertheless, use of the traditional ...polyethylene oxide‐based solid‐state polymer electrolyte is limited due to its inherently low ionic conductivity and narrow electrochemical stability window. Herein, for the first time, we specifically designed a cyanoethyl cellulose‐in‐deep eutectic solvent composite eutectogel as a promising candidate for hybrid solid‐state polymer electrolytes. It is found that the proposed eutectogel electrolyte achieves high ionic conductivity (1.87 × 10−3 S cm−1 at 25°C), superior electrochemical stability (up to 4.8 V), and outstanding lithium plating/striping behavior (low overpotential of 0.04 V at 1 mA cm−2 and 1 mA h cm−2 over 300 h). With the eutectogel‐based solid‐state polymer electrolyte, a 4.45 V LiCoO2/Li metal battery delivers prominent long‐term lifespan (capacity retention of 85% after 200 cycles) and high average Coulombic efficiency (99.5%) under ambient conditions, significantly outperforming the traditional carbonate‐based liquid electrolyte. Our work demonstrates a promising strategy for designing eutectogel‐based solid‐state polymer electrolytes to realize high‐voltage and high‐energy lithium metal batteries.
High‐voltage‐tolerant and ion‐conductive cyanoethyl‐based eutectogel is specifically designed and fabricated as promising solid polymer electrolyte for advanced lithium metal batteries. Benefiting from the stable interfacial chemistry, the 4.45 V LiCoO2/Li metal battery delivered excellent cycling stability and high average Coulombic efficiency. In addition, the cell exhibits outstangding safety under some abuse conditions.
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