RESUMEN
Correction for 'A poly(thymine)-templated fluorescent copper nanoparticle hydrogel-based visual and portable strategy for an organophosphorus pesticide assay' by Jihua Chen et al., Analyst, 2019, 144, 2423-2429, https://doi.org/10.1039/C9AN00017H.
RESUMEN
The past few decades have witnessed biodegradation of pesticides as a significant method in remediation of the environment for its specificity, efficiency and biocompatibility. However, the tolerability and recyclability of the enzymes in pesticide degradation and the development of enzymes that biodegrad pesticides are still urgent problems to be solved so far. Herein, a novel hyper-thermostable and chlorpyrifos-hydrolyzing carboxylesterase EstC was immobilized by biomineralization using zeolitic imidazolate framework (ZIF), one of the metal-organic frameworks (MOFs) with highly diverse structure and porosity. Compared with free enzyme, EstC@ZIF with a cruciate flower-like morphology presented scarcely variation in catalytic efficiency and generally improved the tolerance to organic solvents or detergents. Furthermore, there was scarcely decrease in the catalytic efficiency of EstC@ZIF and it also showed good reusability with about 50% residual activity after 12 continuous uses. Notably, EstC@ZIF could be used in actual water environment with an excellent value of degradation rate of 90.27% in 120 min, and the degradation efficiency remained about 50% after 9 repetitions. The present strategy of immobilizing carboxylesterase to treat pesticide-contaminated water broadens the method of immobilized enzymes on MOFs, and envisions its recyclable applicability in globe environmental remediation.
Asunto(s)
Cloropirifos , Estructuras Metalorgánicas , Plaguicidas , Zeolitas , Carboxilesterasa , Zeolitas/química , Agua , Estructuras Metalorgánicas/químicaRESUMEN
BACKGROUND: Tyrosine kinase inhibitors (TKIs) are mainstays of cancer treatment. However, their clinical benefits are often constrained by acquired resistance. To overcome such outcomes, we have rationally engineered APG-2449 as a novel multikinase inhibitor that is highly potent against oncogenic alterations of anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 receptor tyrosine kinase (ROS1), and focal adhesion kinase (FAK). Here we present the preclinical evaluation of APG-2449, which exhibits antiproliferative activity in cells carrying ALK fusion or secondary mutations. METHODS: KINOMEscan® and LANCE TR-FRET were used to characterize targets and selectivity of APG-2449. Water-soluble tetrazolium salt (WST-8) viability assay and xenograft tumorigenicity were employed to evaluate therapeutic efficacy of monotherapy or drug combination in preclinical models of solid tumors. Western blot, pharmacokinetic, and flow cytometry analyses, as well as RNA sequencing were used to explore pharmacokinetic-pharmacodynamic correlations and the mechanism of actions driving drug combination synergy. RESULTS: In mice bearing wild-type or ALK/ROS1-mutant non-small-cell lung cancer (NSCLC), APG-2449 demonstrates potent antitumor activity, with correlations between pharmacokinetics and pharmacodynamics in vivo. Through FAK inhibition, APG-2449 sensitizes ovarian xenograft tumors to paclitaxel by reducing CD44+ and aldehyde dehydrogenase 1-positive (ALDH1+) cancer stem cell populations, including ovarian tumors insensitive to carboplatin. In epidermal growth factor receptor (EGFR)-mutated NSCLC xenograft models, APG-2449 enhances EGFR TKI-induced tumor growth inhibition, while the ternary combination of APG-2449 with EGFR (osimertinib) and mitogen-activated extracellular signal-regulated kinase (MEK; trametinib) inhibitors overcomes osimertinib resistance. Mechanistically, phosphorylation of ALK, ROS1, and FAK, as well as their downstream components, is effectively inhibited by APG-2449. CONCLUSIONS: Taken together, our studies demonstrate that APG-2449 exerts potent and durable antitumor activity in human NSCLC and ovarian tumor models when administered alone or in combination with other therapies. A phase 1 clinical trial has been initiated to evaluate the safety and preliminary efficacy of APG-2449 in patients with advanced solid tumors, including ALK+ NSCLC refractory to earlier-generation ALK inhibitors. TRIAL REGISTRATION: Clinicaltrial.gov registration: NCT03917043 (date of first registration, 16/04/2019) and Chinese clinical trial registration: CTR20190468 (date of first registration, 09/04/2019).
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neoplasias Ováricas , Animales , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Ensayos Clínicos Fase I como Asunto , Receptores ErbB/genética , Receptores ErbB/uso terapéutico , Femenino , Proteína-Tirosina Quinasas de Adhesión Focal , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Ratones , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas , Proteínas Proto-Oncogénicas/genética , Proteínas Tirosina Quinasas Receptoras/metabolismoRESUMEN
An effective and precise electrochemiluminescence resonance energy transfer (ECL-RET), including the efficient regulation over the proximity of a donor and an acceptor and the reliable stimuli responsive as well as the avoidance of undesirable probes leakage, etc., is significant for the development of an accurate and sensitive ECL detection method; yet, the current literature in documentation involves only a limited range of such ECL-RET systems. Herein, we propose an ECL-RET strategy with dually quenched ultralow background signals and a dual-stimuli responsive, accurate signal output for the ultrasensitive and reliable detection of anatoxin-a (ATX-a). The dual quenching is accomplished by an integrated ECL-RET probe of metal organic frameworks (MOFs) encapsulated into Ru(bpy)32+ (Ru-MOF) (donor) coated with silver nanoparticles (AgNPs) shell (acceptor 1) and close proximity with DNA-ferrocene (Fc) (acceptor 2). Multistimuli responsive DNAzyme facilitated the accurate signal switch by both target ATX-a and hydrogen peroxide (H2O2). Because of the specific recognition of the aptamer toward ATX-a, an intricate design of the DNA sequence enabled the exposure of the Ag+-dependent DNAzyme sequence and H2O2 in situ generated Ag+ triggering a catalytic cleavage reaction to freely release the two ECL-RET energy acceptors, thus switching the ECL signal significantly and achieving ultrasensitive detection. It is noteworthy that AgNPs are key in this ECL-RET strategy, serving both as the gate-keepers for avoiding ECL probes leakage and also the ECL energy acceptors, and mostly importantly serving as the redox substrate for the subsequent DNAzyme catalytic signal switch. The proposed ECL-RET aptasensor for ATX-a detection displayed splendid monitoring performance with a quite low detection limit of 0.00034 mg mL-1. This sensor not only led to the development of a dual-quenching ECL-RET system but also provided meaningful multistimuli responsive ECL biosensing platform construction, which shows a promising application prospect in complicated sample analysis.
Asunto(s)
ADN Catalítico , Nanopartículas del Metal , Toxinas de Cianobacterias , Técnicas Electroquímicas , Transferencia de Energía , Peróxido de Hidrógeno , Mediciones Luminiscentes , Plata , TropanosRESUMEN
Endowing specificity and controllability with the electrochemiluminescence (ECL) thermosensitive hydrogels is vitally crucial to expanding their sensing applications. Herein, a novel photocontrolled thermosensitive electrochemiluminescence hydrogel (PT-ECL hydrogel) sensing platform with sufficient simplicity, specificity, and precise controllability is proposed, for the first time, by the integration of Ru(bpy)32+ (bpy = 2,2'-bipyridine) derivatives (signal reporter), split aptamers (recognition unites), and Au nanorods (AuNRs) (photothermal energy converter) into the poly(N-isopropylacrylamide) (pNIPAM) matrix. In the presence of the model target isocarbophos (ICP), the conjugation of two split aptamers initiated the ECL-resonance energy transfer (ECL-RET) between the Au nanorods and the Ru(bpy)32+ centers. Surprisingly, under the irradiation of near-infrared (NIR) light, the photothermal effect of AuNRs prompted the shrinkage of the hydrogel, resulting in the enhancement of the ECL-RET and further â¼7 times signal amplification. Consequently, the PT-ECL hydrogel sensing platform performed well for ICP detection with a low detection limit of 20 pM (S/N = 3) and a wide linear range from 50 pM to 4 µM, with great stability and repeatability. Obviously, the results showed that AuNRs utilized in this study served the role as not only the ECL-RET acceptor but also the photothermal converter to prompt the phase change of the PT-ECL hydrogel precisely and simply controlled by NIR light. Use of the proposed PT-ECL hydrogel detection scheme is a first step toward enabling a newly upgraded highly sensitive and selective hydrogel-based assay and also paving the way for the application of smart photothermal reagents.
RESUMEN
In this work, we demonstrated an ultrasensitive detection platform for polychlorinated biphenyls (PCBs) based on DNA microcapsules and a nonlinear hybridization chain reaction (NHCR). In the process, first, electrochemical signal molecules (Methylene Blue, MB) were sealed in the prepared DNA microcapsules. In the presence of PCB-72, DNA microcapsules could be dissociated with the conjugation of the aptamer and target, and meanwhile, the released DNA strand could initiate the NHCR and trigger the chain branching growth of DNA dendrimers. Because the released MBs were intercalated into the DNA dendrimer, enhanced electrochemical responses could be detected. This method exhibited ultrahigh sensitivity to PCB-72 with a detection limit of 0.001 ng mL-1. Furthermore, the present aptasensor was also capable of discriminating different PCB congeners. Therefore, the devised label-free and enzyme-free amplification electrochemical aptasensor strategy has great potential for the detection of PCB-72 in real samples, and this strategy may also become an attractive alternative for sensitive and selective small molecule, protein, nucleic acid and nuclease activity detection.
Asunto(s)
Aptámeros de Nucleótidos/metabolismo , Técnicas Biosensibles/métodos , ADN/química , Límite de Detección , Bifenilos Policlorados/análisis , Aptámeros de Nucleótidos/química , Aptámeros de Nucleótidos/genética , Cápsulas , Electroquímica , Azul de Metileno/química , Técnicas de Amplificación de Ácido Nucleico , Hibridación de Ácido Nucleico , Bifenilos Policlorados/químicaRESUMEN
Since fluorescence assays with high sensitivity for organophosphorus pesticides (OPs) are urgently required to protect the ecosystem and prevent disease, an environmentally friendly and label-free fluorescent probe is desirable. Herein, a poly-thymine30 DNA-templated copper nanoparticle (poly T30-Cu NPs) hydrogel fluorescent probe was explored for the construction of an OPs sensing platform via tyrosinase (TYR) enzyme-controlled quenching. Initially, TYR can efficiently quench the fluorescence of poly T30-Cu NPs; however, when OPs are mixed with a certain amount of TYR, the fluorescence of poly T30-Cu NPs can be recovered. Based on this phenomenon, we designed a functionalized hydrogel based on poly T30-Cu NPs for portable and visible detection of OPs with high sensitivity and selectivity. This proposed fluorescent platform was demonstrated to enable rapid detection of OPs (paraoxon as the model analyte) and provide excellent sensitivity with a detection limit of 3.33 × 10-5 ng µL-1 and a linear range of 1.0 × 10-4-1.0 ng µL-1. The fluorescent probe does not require a sophisticated synthesis and labeling process; in addition, it is environmentally friendly because of the presence of a biotemplate of DNA and biocompatible copper. Moreover, the functional hydrogel combines the features of portability, visualization, fast signal response and environmental anti-interference that make the proposed strategy more feasible in complex practical detection.
RESUMEN
A fluorescent probe for H2O2 is described. It is composed of MnO2 nanosheets and 5-carboxyfluorescein and was characterized by fluorescence, transmission electron microscopy, ultraviolet-visible absorption spectra, energy dispersive X-ray and Fourier transform infrared spectroscopy. The probe, with fluorescence excitation/emission maxima at 490/518 nm, responds to H2O2 in the 1 to 200 µM concentration range and has a 0.33 µM detection limit. The probe was used in enzymatic assays for glucose and cholesterol by using the respective oxidases which produce H2O2. Responses are linear in the concentration range from 0.5 to 200 µM in case of glucose, and from 1 to 300 µM in case of cholesterol. The method was applied to quantify glucose and cholesterol in (spiked) serum samples. Graphical abstract Schematic presentation of the principle based on hydrogen peroxide-induced degradation of MnO2 nanosheet-FAM complex for detection of H2O2 (a), glucose and cholesterol (b).
Asunto(s)
Glucemia/análisis , Colesterol/sangre , Fluoresceínas/química , Fluorometría/métodos , Peróxido de Hidrógeno/sangre , Compuestos de Manganeso/química , Óxidos/química , Humanos , Límite de Detección , Nanoestructuras/químicaRESUMEN
In this paper, a novel colorimetric method for the detection of alkaline phosphatase (ALP) and pyrophosphate (PPi) was designed based on a Cu(2+)-horseradish peroxidase (HRP)-3,3',5,5'-tetra-methylbenzidine (TMB)-H2O2 system. In the presence of ALP, l-ascorbic acid-2-phosphate (AAP) could be hydrolyzed to ascorbic acid which could reduce Cu(2+) to Cu(+) to inhibit the enzymatic activity of HRP in the colorimetric system. The change in absorbance was found to be proportional to the ALP concentration with a linear detection range and a limit of detection of 5.4 mU mL(-1). In the presence of PPi, because Cu(2+) was chelated by PPi, the conversion of Cu(ii) by AA was effectively inhibited. The color of the HRP-TMB-H2O2 system with Cu(2+) showed blue. The HRP-TMB-H2O2 system with the Cu(2+) colorimetric system could also detect PPi with a satisfying result. In summary, this method possesses sensitivity, reproducibility, and cost-effectiveness without labelling and separation and the use of a colorimetric method is more in line with the requirements of on-site detection and green chemistry.
Asunto(s)
Fosfatasa Alcalina/análisis , Colorimetría/métodos , Cobre/química , Difosfatos/análisis , Peroxidasa de Rábano Silvestre/química , Peróxido de Hidrógeno/química , Reproducibilidad de los ResultadosRESUMEN
Development of strategies for the sensitive and selective detection of the folate receptor (FR) that are simple and low cost is of great importance for assessing cancer therapeutics due to its crucial role in physiological, pharmacological and pathological processes. In this paper, gold nanoparticle (AuNP)-based novel ratiometric colorimetry for the detection of the folate receptor (FR) is proposed based on terminal protection of small-molecule-linked DNA. The single-stranded DNA (ssDNA) terminally tethered to folic acid (FA) is protected from degradation by exonuclease I (Exo I) when the FA moiety is bound to FR. The hybridization between FR-protected DNA and DNA-functionalized Au NPs generated a red-to-purple colour change, allowing the visual detection of FR. The detection limit of FR can be as low as 0.33 ng mL(-1) with the naked eye. It provides a promising strategy for visual detection of the binding event of FA to its protein receptor-FR with advantages such as simplicity, high selectivity, and a wide linear range.
Asunto(s)
Colorimetría/métodos , Receptores de Folato Anclados a GPI/sangre , Ácido Fólico/química , Oro/química , Ácidos Nucleicos Inmovilizados/química , Nanopartículas del Metal/química , ADN de Cadena Simple/química , Receptores de Folato Anclados a GPI/análisis , Humanos , Límite de Detección , Nanopartículas del Metal/ultraestructura , Hibridación de Ácido NucleicoRESUMEN
Thioflavin T (ThT), as one of the most exciting fluorogenic molecules, boasts the "molecular-rotor" ability to induce DNA sequences containing guanine repeats to fold into G-quadruplex structures. It has been demonstrated to sense this change by its remarkable fluorescence enhancement. In this work, taking T4 polynucleotide kinase (PNK) as a model, the ThT/G-quadruplex based platform and λexonuclease (λexo) cleavage reaction were combined to design a label-free "turn-on" strategy for fast, simple and accurate detection of T4 PNK activity and its inhibition. In the presence of T4 PNK, the designed thioflavin T based molecular beacon (TMB) DNA probe could be phosphorylated and then digested by the cleavage of λexo, releasing the G-quartets. These then bound to ThT to form ThT/G-quadruplexes with an obvious fluorescence generation, for the "turn-on" detection of T4 PNK. In comparison to traditional methods, the proposed TMB probe is convenient, requiring no sophisticated labeling and separation processes and displaying high analytical performance. It exhibits a satisfying detection result for the activity of T4 PNK with a low detection limit of 0.001 U mL(-1). This is not only meaningful for further research on disease-related biochemical processes, but also valuable for molecular-target therapies.
Asunto(s)
Bacteriófago T4/enzimología , Sondas de Oligonucleótidos/química , Polinucleótido 5'-Hidroxil-Quinasa/antagonistas & inhibidores , Polinucleótido 5'-Hidroxil-Quinasa/metabolismo , Fluorescencia , Humanos , Límite de Detección , Coloración y EtiquetadoRESUMEN
Luminescent silver nanoclusters (AgNCs) were anchored by designed oligonucleotides, acting as fluorescent labels. They hybridized with specific nucleic acid targets to form a supersandwich structure resulting in the fluorescence intensity of the DNA/AgNCs decreasing linearly with respect to the concentration of the target DNA.
Asunto(s)
ADN/química , Mediciones Luminiscentes/métodos , Nanopartículas del Metal/química , Ácidos Nucleicos/análisis , Plata/química , Límite de Detección , Mediciones Luminiscentes/normasRESUMEN
In this paper, horseradish peroxidase-mimicking DNAzyme (HRP-DNAzyme) and Prussian blue (PB)-gold (Au) nanocomposites were designed as versatile electrochemical sensing platforms for the amplified detection of DNA, Hg(2+) and adenosine triphosphate (ATP). By the conjugation of the target probe with the capture probe, a conformational change resulted in the formation of HRP-DNAzyme on the PB-Au modified electrode. The redox of HRP-DNAzyme (red) was efficiently carried out in the presence of H2O2, in which PB acted as a mediator stimulating the biocatalytic functions of HRP-DNAzyme and actuated a catalytic cycle bringing an amplified signal. Specific recognition of the target DNA, Hg(2+) and ATP allowed selective amperometric detection of the target molecule. The detection limits of DNA, Hg(2+) and ATP were 50 nM, 30 pM and 3 nM, respectively. The highlight of this work is that the catalytic cycle between PB-Au nanocomposites and HRP-DNAzyme was adequately utilized in the amplification platform for versatile sensing. The novel electrocatalytic biosensor involving only one-step incubation exhibited a wide linear range, low detection limit, and satisfactory selectivity and operational stability. The proposed approach provided an ease-of-use and universal reporting system with a simple design and easy operations.
Asunto(s)
Adenosina Trifosfato/análisis , Técnicas de Química Analítica/métodos , ADN/análisis , Técnicas Electroquímicas , G-Cuádruplex , Hemina/química , Mercurio/análisis , Nanocompuestos/química , Catálisis , ADN Catalítico/química , ADN Catalítico/metabolismo , Electrodos , Ferrocianuros/química , Oro/química , Peroxidasa de Rábano Silvestre/química , Peroxidasa de Rábano Silvestre/metabolismo , Peróxido de Hidrógeno/química , Iones/químicaRESUMEN
In this paper, we have designed a signal amplified method for the electrochemical determination of polynucleotide kinase activity. It is based on (a) the peroxidase-like activity of magnetite microspheres (MNPs), (b) the specific recognition capabilities of titanium dioxide (TiO2) with the phosphate groups of the capture probe and (c) the DNA dendrimer structure for signal amplification. MNPs coated with TiO2 (TMNPs) were prepared and characterized by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy. TMNP-DNA dendrimers were formed by the hybridization of captured nucleic acids with a link probe. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were carried out to study the electrocatalytic process. The formation of the TMNP-DNA dendrimer structures was related to the phosphorylated capture probe and further to the activity of polynucleotide kinase, which was the base of the polynucleotide kinase detection. The TMNP-DNA dendrimer based biosensor showed sensitive detection of polynucleotide kinase with a satisfying result; a low detection of 0.003 U mL(-1) and wide linear range of 0.01 to 30 U mL(-1) were achieved. Additionally, the present TMNP-DNA dendrimer based biosensor also demonstrated excellent selectivity, stability and reproducibility.
Asunto(s)
Bacteriófago T4/enzimología , Técnicas Electroquímicas/instrumentación , Oro/química , Nanopartículas/química , Polinucleótido 5'-Hidroxil-Quinasa/metabolismo , Titanio/química , ADN/química , Dendrímeros/química , Electrodos , Pruebas de Enzimas/instrumentación , Diseño de Equipo , Humanos , Límite de Detección , Fenómenos Magnéticos , Microesferas , Polinucleótido 5'-Hidroxil-Quinasa/sangre , Reproducibilidad de los ResultadosRESUMEN
Endowing current artificial chemical reactions (ACRs) with high specificity and intricate activation capabilities is crucial for expanding their applications in accurate bioimaging within living cells. However, most of the reported ACR-based evaluations relied on either single biomarker stimuli or dual activators without obvious biological relevance, still limiting their accuracy and fidelity. Herein, taking the metal-ion-dependent DNAzyme cleavage reaction as a model ACR, two regulators, glutathione (GSH) and telomerase (TE) activated DNAzyme cleavage reactions, were exploited for precise discrimination of cancerous cells from normal cells. DNA probe was self-assembled into the ZIF-90 nanoparticle framework to construct coordination-driven nanoprobes. This approach enhances the stability and specificity of tumor imaging by utilizing biomarkers associated with rapid tumor proliferation and those commonly overexpressed in tumors. In conclusion, the research not only paves the way for new perspectives in cell biology and pathology studies but also lays a solid foundation for the advancement of biomedical imaging and disease diagnostic technologies.
Asunto(s)
ADN Catalítico , ADN Catalítico/química , ADN Catalítico/metabolismo , Humanos , Nanopartículas/química , Glutatión/metabolismo , Glutatión/química , Telomerasa/metabolismo , Neoplasias/diagnóstico por imagen , Neoplasias/metabolismo , Línea Celular Tumoral , Imagen ÓpticaRESUMEN
Ratiometric imaging of tumor-related mRNA is significant, yet spatiotemporally resolved regulation on the ratiometric signals to avoid non-specific activation in the living cells remains challenging. Herein, orthogonally sequential activation of concatenated DNAzyme circuits is, first, developed for Spatio Temporally regulated Amplified and Ratiometric (STAR) imaging of TK1 mRNA inside living cells with enhanced reliability and accuracy. By virtue of the synthesized CuO/MnO2 nanosheets, orthogonally regulated self-powered DNAzyme circuits are operated precisely in living cells, sequentially activating two-layered DNAzyme cleavage reactions to achieve the two ratiometric signal readouts successively for reliable monitoring of low-abundance mRNA in living cells. It is found that the ratiometric signals can only be derived from mRNA over-expressed tumor cells, also irrespective of probes' delivery concentration. The presented approach could provide new insight into orthogonally regulated ratiometric systems for reliable imaging of specific biomarkers in living cells, benefiting disease precision diagnostics.
Asunto(s)
Técnicas Biosensibles , ADN Catalítico , Humanos , ARN Mensajero , Compuestos de Manganeso , Reproducibilidad de los Resultados , Óxidos , Técnicas Biosensibles/métodosRESUMEN
Targeted assembly of nanoparticles in biological systems holds great promise for disease-specific imaging and therapy. However, the current manipulation of nanoparticle dynamics is primarily limited to organic pericyclic reactions, which necessitate the introduction of synthetic functional groups as bioorthogonal handles on the nanoparticles, leading to complex and laborious design processes. Here, we report the synthesis of tyrosine (Tyr)-modified peptides-capped iodine (I) doped CuS nanoparticles (CuS-I@P1 NPs) as self-catalytic building blocks that undergo self-propelled assembly inside tumour cells via Tyr-Tyr condensation reactions catalyzed by the nanoparticles themselves. Upon cellular internalization, the CuS-I@P1 NPs undergo furin-guided condensation reactions, leading to the formation of CuS-I nanoparticle assemblies through dityrosine bond. The tumour-specific furin-instructed intracellular assembly of CuS-I NPs exhibits activatable dual-modal imaging capability and enhanced photothermal effect, enabling highly efficient imaging and therapy of tumours. The robust nanoparticle self-catalysis-regulated in situ assembly, facilitated by natural handles, offers the advantages of convenient fabrication, high reaction specificity, and biocompatibility, representing a generalizable strategy for target-specific activatable biomedical imaging and therapy.
Asunto(s)
Nanopartículas , Neoplasias , Humanos , Furina , Fototerapia , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Nanopartículas/química , Catálisis , Cobre/químicaRESUMEN
In the present study, based on multifunctional Dual-Hairpin DNA structure, a simple, fast and high sensitive assay for the detection of DNA, thrombin and adenosine triphosphate (ATP) was demonstrated. DNA sequence labeled with methylene blue (MB), which was designed as single-stranded DNA (ssDNA) matching with target DNA, thrombin, or ATP aptamer, hybridized to the adjunct probe and formed the dual-hairpin structure on the electrode. With the hybridization of adjunct probe and the hairpin-like capture probe in the stem region, the dual-hairpin was formed with outer and inner hairpins. By the conjugation of the target probe with the adjunct probe in the outer hairpin, the adjunct probe divorced from the dual-hairpin structure. The adjunct probe with signal molecules MB, attaching near or divorcing far from the electrode, produced electrochemical signal change and efficient electron transfer due to the fact that it was in proximity to the electrode. However, upon hybridization with the perfect match target, the redox label with the target probe was forced away from the modified electrode, thus resulting in the change of the Dual-Hairpin DNA conformation, which enables impedance of the efficient electron transfer of MB and, consequently, a detectable change of the electrochemical response. In addition, another highlight of this biosensor is its regenerability and stability owing to the merits of structure. Also, based on this Dual-Hairpin platform, the detection limits of DNA, thrombin, and ATP were 50 nM, 3 pM, and 30 nM, respectively. Moreover, this pattern also demonstrated excellent regenerability, reproducibility, and stability. Additionally, given to its ease-of-use, simplicity in design, easy operations, as well as regenerability and stability, the proposed approach may be applied as an excellent design prompter in the preparation of other molecular sensors.
Asunto(s)
Adenosina Trifosfato/análisis , Técnicas Biosensibles/métodos , ADN/análisis , ADN/genética , Secuencias Invertidas Repetidas , Trombina/análisis , Secuencia de Bases , Cocaína/análisis , ADN/química , Electroquímica , Modelos Moleculares , Conformación de Ácido Nucleico , Factores de TiempoRESUMEN
Ag(+) is known to bind very strongly with cytosine-cytosine (C-C) mismatches in DNA duplexes to form C-Ag(+)-C base pairs. Exonuclease III (Exo III) can catalyze the stepwise removal of mononucleotides of duplex DNA. In this work, we study Exo III activity on DNA hybrids containing C-Ag(+)-C base pairs. Our experiments show that Ag(+) ions could intentionally trigger the activity of Exo III towards a designed cytosine-rich DNA oligonucleotide (C-rich probe) by the conformational change of the probe. Our sensing strategy uses this conformation-dependent activity of Exo III, which is controlled through the cyclical shuffling of Ag(+) ions between the solid DNA hybrid and the solution phase. This interesting conversion has led to the development of an ultrasensitive detection platform for Ag(+) ions with a detection limit of 0.03 nM and a total assay time possible within minutes. This simple detection strategy could also be used for the detection of other metal ions which exhibit specific interactions with natural or synthetic bases.
Asunto(s)
Técnicas Biosensibles/instrumentación , Citosina/química , Técnicas Electroquímicas/normas , Exodesoxirribonucleasas/química , Plata/química , Ciclización , Límite de Detección , Técnicas de Amplificación de Ácido NucleicoRESUMEN
A facile and low-cost approach has been developed to fabricate porous CuO nanobelts directly grown on a Cu substrate. The as-prepared CuO samples can be directly used as integrated electrodes for lithium-ion batteries and pseudo-supercapacitors without the addition of other ancillary materials such as carbon black or a binder to enhance electrode conductivity and cycling stability. The unique nanostructural features endow them with excellent electrochemical performance as demonstrated by high capacities of 640 mA h g(-1) after 100 cycles at 0.2 C rate and an excellent specific capacitance of 340 F g(-1), which corresponds to the energy density of 45 W h kg(-1). The cyclability of the electrode demonstrates only a 10-15% loss in capacitance over 5000 cycles.