New Transferrin Receptor-Targeted Peptide-Doxorubicin Conjugates: Synthesis and In Vitro Antitumor Activity.

Poor selectivity to tumor cells is a major drawback in the clinical application of the antitumor drug doxorubicin (DOX). Peptide-drug conjugates (PDCs) constructed by modifying antitumor drugs with peptide ligands that have high affinity to certain overexpressed receptors in tumor cells are increasingly assessed for their possibility of tumor-selective drug delivery. However, peptide ligands composed of natural L-configuration amino acids have the defects of easy enzymatic degradation and insufficient biological stability. In this study, two new PDCs (LT7-SS-DOX and DT7-SS-DOX) were designed and synthesized by conjugating a transferrin receptor (TfR) peptide ligand LT7 (HAIYPRH) and its retro-inverso analog DT7 (hrpyiah), respectively, with DOX via a disulfide bond linker. Both conjugates exhibited targeted antiproliferative effects on TfR overexpressed tumor cells and little toxicity to TfR low-expressed normal cells compared with free DOX. Moreover, the DT7-SS-DOX conjugate possessed higher serum stability, more sustained reduction-triggered drug release characteristics, and stronger in vitro antiproliferative activity as compared to LT7-SS-DOX. In conclusion, the coupling of antitumor drugs with the DT7 peptide ligand can be used as a promising strategy for the further development of stable and efficient PDCs with the potential to facilitate TfR-targeted drug delivery.

Baicalin ameliorates the gut barrier function and intestinal microbiota of broiler chickens.

The deoxynivalenol (DON)-contaminated feeds can impair chicken gut barrier function, disturb the balance of the intestinal microbiota, decrease chicken growth performance and cause major economic loss. With the aim of investigating the ameliorating effects of baicalin on broiler intestinal barrier damage and gut microbiota dysbiosis induced by DON, a total of 150 Arbor Acres broilers are used in the present study. The morphological damage to the duodenum, jejunum, and ileum caused by DON is reversed by treatment with different doses of baicalin, and the expression of tight junction proteins (ZO-1, claudin-1, and occludin) is also significantly increased in the baicalin-treated groups. Moreover, the disturbance of the intestinal microbiota caused by DON-contaminated feed is altered by baicalin treatment. In particular, compared with those in the DON group, the relative abundances of Lactobacillus, Lachnoclostridium, Ruminiclostridium and other beneficial microbes in the baicalin-treated groups are significantly greater. However, the percentage of unclassified_f__Lachnospiraceae in the baicalin-treated groups is significantly decreased in the DON group. Overall, the current results demonstrate that different doses of baicalin can improve broiler intestinal barrier function and the ameliorating effects on broiler intestinal barrier damage may be related to modulations of the intestinal microbiota.

Bromine-mediated strategy endows efficient electrochemical oxidation of amine to nitrile.

Conventional methods for nitrile synthesis bring inherent environmental risks due to their reliance on oxidants and harsh reaction conditions. Meanwhile, direct electrooxidation of amines to nitriles suffers from low current density. In this study, we propose an innovative indirect electrooxidation strategy for nitrile formation, mediated by Br-/Br2, utilizing a highly efficient CoS2/CoS@Graphite Felt (GF) electrode. Notably, the anodic nitrile generation can be synergistically coupled with the cathodic hydrogen evolution reaction (HER). Through meticulous optimization of reaction parameters, we achieve an impressive 98% selectivity for octanenitrile at a current density of 60 mA cm-2 with a remarkable faradaic efficiency (FE) of 87%. Furthermore, our approach demonstrates excellent versatility, as we successfully evaluate both aliphatic and aromatic primary amines, highlighting its promising potential for practical applications in the field.

Metal-organic framework integrated hydrogel bioreactor for smart detection of metal ions.

Bioreactors with environment responsiveness for smart detection has attracted widespread interest. Bioreactors that operate in liquid have excellent reaction speed and sensitivity, and those that operate at a solid interface have unique portability and stability. However, bioreactors that can simultaneously take advantage of both properties are still limited. Here, we developed a metal-organic framework (MOF) integrated hydrogel bioreactor that can accommodate both solid and liquid properties by using a hydrogel as a quasi-liquid medium. To enhance the stability and intelligence of the hydrogel bioreactor, we have opted for the utilization of europium metal-organic framework (Eu-MOF) as the optical output to withstand long-term storage challenges, and DNA as the highly programmable substance for intelligent target response. On this basis, smart detection of metal ions and biological micro-molecules have been achieved. Notably, this quasi-liquid hydrogel bioreactor has effectively tackled the intrinsic issues of inadequate dispersion stability of Eu-MOF in liquid systems and poor stability of DNA against environmental interference. Moreover, this MOF integrated hydrogel bioreactor has been applied to the construction of a portable hydrogel bioreactor, which enables platform-free and arrayed target detection via a smartphone, providing a new perspective for further promoting the application of quasi-liquid hydrogel bioreactors and intelligent nanobiological sensors.

Ru nanoclusters anchored on boron- and nitrogen-doped carbon for a highly efficient hydrogen evolution reaction in alkaline seawater.

Electrochemical seawater splitting is an intriguing strategy for green hydrogen production. Constructing advanced electrocatalysts for the hydrogen evolution reaction (HER) in seawater is extremely demanded for accelerating the sluggish kinetic process. Herein, a Ru nanocluster anchored on boron- and nitrogen-doped carbon (Ru/NBC) catalyst was successfully synthesized for the HER in alkaline/seawater electrolytes. Remarkably, Ru/NBC exhibits outstanding activity and durability, delivering low overpotentials@10 mA cm-2 in 1.0 M KOH (30 mV) and 1.0 M KOH + seawater electrolyte (35 mV), outperforming Pt/C, Ru/NC, Ru/BC and Ru/C. Additionally, Ru/NBC also provides a high specific activity of 0.093 mA cm-2ECSA at an overpotential of 150 mV, which is higher than those of Ru/NC, Ru/BC and Ru/C, respectively. Density functional theory calculation results demonstrate that the Ru-B formed interfacial chemical bond can regulate the electronic structure of Ru active sites of Ru/NBC, which can facilitate the adsorption of water and hydrogen in alkaline media. This work provides a feasible strategy to fabricate outstanding electrocatalysts for the HER in alkaline/alkaline seawater electrolytes.

(Eu-MOF)-derived Smart luminescent sensing for Ultrasensitive on-site detection of MiR-892b.

MicroRNAs (miRNAs) are important biomacromolecules used as biomarkers for the diagnosis of several diseases. However, current detection strategies are limited by expensive equipment and complicated procedures. Here, we develop a portable, sensitive, and stable (Eu-MOF)-based sensing platform to detect miRNA via smartphone. The Eu-MOF absorbs the carboxyfluorescein (FAM)-tagged probe DNA (pDNA) to generate hybrid pDNA@Eu-MOF, which can efficiently quench the fluorescence of FAM through a photoinduced electron transfer (PET) process. When integrated with a smartphone, the nonemissive pDNA@ Eu-MOF hybrid could be utilized as a portable and sensitive platform to sense miRNA (miR-892b) with a detection limit of 0.32 pM, which could be even distinguished by the naked eye. Moreover, this system demonstrates high selectivity for identifying miRNA family members with single-base mismatches. Furthermore, the expression levels of miRNA in cancer cell samples could be analyzed accurately. Therefore, the proposed method offers a promising guideline for the design of MOF-based sensing strategies and expands their potential applications for diagnostic purposes.

Protective effecs of baicalin magnesium on non-alcoholic steatohepatitis rats are based on inhibiting NLRP3/Caspase-1/IL-1ß signaling pathway.

Baicalin magnesium is a water-soluble compound isolated from the aqueous solution by Scutellaria baicalensis Georgi. Preliminary experiments have demonstrated that baicalin magnesium can exert protective effects against acute liver injury in rats induced by carbon tetrachloride or lipopolysaccharide combined with d-galactose by regulating lipid peroxidation and oxidative stress. The aim of this study was to investigate the protective effect of baicalin magnesium on non-alcoholic steatohepatitis (NASH) in rats and to elucidate the underlying mechanisms. NASH was induced through a high-fat diet (HFD) for 8 weeks, and Sprague-Dawley rats were intravenously injected with baicalin magnesium, baicalin, and magnesium sulfate for 2 weeks, respectively. Serum was obtained for biochemical analyses and the determination of oxidative stress indicators. Liver tissues were collected for use in liver index assessment, histopathological examination, inflammatory factor analysis, and protein and gene expression analysis. The results revealed that baicalin magnesium markedly improved HFD-induced lipid deposition, inflammatory response, oxidative stress, and histopathological impairments. And baicalin magnesium may exert a protective effect on NASH rats by inhibiting the NLR family pyrin domain involving the 3 (NLRP3)/caspase-1/interleukin (IL)-1ß inflammatory pathway. Additionally, the effect of baicalin magnesium was remarkably superior to that of equimolar baicalin and magnesium sulfate in regard to ameliorating NASH symptoms. In conclusion, the findings suggested that baicalin magnesium may represent a potential drug for the treatment of NASH.

Accelerated Fenton degradation of azo dye wastewater via a novel Z-scheme CoFeN-g-C3N4 heterojunction photocatalyst with excellent charge transfer under visible light irradiation.

A novel Z-scheme heterostructure photocatalyst, CoFeN-g-C3N4 (CFN-CN), was prepared by a simple strategy, and its heterostructure and a photo-Fenton system were used to synergistically catalyze the degradation of azo dyes. The experimental results showed that the CFN-CN1 heterojunction exhibited superior photocatalytic degradation performance, and the degradation rate of Methyl Orange (MO) reached 96.8% in 40 min. The degradation rate constants were 11.8 and 2.81 times those of CN and CFN, respectively. CFN-CN1 also shows excellent catalytic degradation performance for other azo dyes (Congo Red (CR), Acid Orange 7 (AO7), Mordant Black 17 (MB17) and Acid Red B (ARB)), and the degradation efficiencies all exceeded 90%. Furthermore, the addition of inorganic anions (Cl-, HCO3- and SO42-) affects the degradation of azo dyes, especially HCO3- which significantly promotes the degradation of MO. The radical trapping experiments and EPR results indicated that superoxide radicals (˙O2-) and hydroxyl radicals (˙OH) were the main active species. The above research reveals that the CFN-CN heterojunction synergistic photo-Fenton system may provide new hints for the degradation and removal of azo dyes from wastewater.

The Piezo-Fenton synergistic effect of ferroelectric single-crystal BaTiO3 nanoparticles for high-efficiency catalytic pollutant degradation in aqueous solution.

Nano-ferroelectric materials have excellent piezoelectric performance and can degrade organic dye by ultrasonic vibration in an aqueous solution. Here, BaTiO3 (BT) nanoparticles were prepared by a sol-gel/hydrothermal method and further applied in dye degradation in wastewater. BT nanoparticles exhibited excellent catalytic performance for organic dye molecule degradation through the piezo-Fenton synergistic effect. It was found that both the degradation efficiency and reaction rate were boosted by the increase of the molecular weight of organic dyes. The degradation efficiency toward different organic dyes exhibited a trend of CR > ABK > TH > RhB > MB > MO. For example, a high piezo-Fenton-catalytic degradation ratio of 82.8% at 5 min and 0.337 min-1 rate constant were achieved for the CR dye solution (10 mg L-1), which were 3.2 and 6.4 times the corresponding values of piezo-catalytic only degradation. These results mainly originate from the intrinsic properties of BT nanoparticles that can enhance the separation of charge and promote the formation of hydrogen peroxide (H2O2) and hydroxyl radicals (·OH) under ultrasonic vibration. Furthermore, the reaction of Fe(II) with H2O2 can further enhance the formation of ·OH, which can accelerate the degradation of organic dyes. These results indicate that the piezo-Fenton synergistic effect may provide a new clue for the development of the wastewater treatment field under mechanical vibration.

Smartphone-Based Pure DNAzyme Hydrogel Platform for Visible and Portable Colorimetric Detection of Cell-Free DNA.

Cell-free DNA (cfDNA), as a tumor marker, is of great importance for the diagnosis of cancer and targeted therapy. However, the need for huge analytical instruments for cfDNA analysis has restricted its practical applications, especially in rural areas and third-world countries. Herein, a portable and visual smartphone-based DNAzyme hydrogel platform is developed for cfDNA detection. The target cfDNA triggers rolling circle amplification to produce a G-quadruplex-comprised DNA hydrogel with an horseradish peroxidase (HRP)-like catalytic function, which further catalyzes the chromogenic substrate to generate a visible output signal. Notably, the naked-eye detection of cfDNA can be realized by the macroscale visibility and catalytic ability of the DNA hydrogel. The linear range of the DNAzyme hydrogel platform for cfDNA detection is 0.1 pM-1500 nM with a detection limit of 0.042 pM. Moreover, this platform is exploited for the detection of cfDNA in spiked human serum with favorable sensitivity and recovery. Therefore, the DNAzyme hydrogel platform provides highly promising potential for testing other nucleic acid biomarkers.

Modulating carbon dioxide activation on carbon nanotube immobilized salophen complexes by varying metal centers for efficient electrocatalytic reduction.

Electrocatalytic CO2 reduction (ECR) into valuable chemicals, especially driven by renewable energy, presents a promising pattern to realize carbon neutrality. Site-isolated metal complexes flourish in the area of ECR as single-atom-like catalysts because of their competent and tailorable activity. In this study, salophen-based metal (Fe, Co, Ni and Cu) complexes were anchored onto carbon nanotubes (CNTs) to construct efficient catalysts for electrochemically converting CO2 to CO. Both experimental and theoretical results verified that CO2 activation was the rate-determining step for the catalytic performance of these hybrid molecular catalysts. The coordinate activation ability can be manipulated by varying the metal centers. The as-synthesized Fe-salophen hybrid CNT (Fe-salophen/CNT) shows the best activity and selectivity of -13.24 mA·cm-2 current density with 86.8% Faradaic efficiency for generating CO (FECO) at -0.76 V vs. RHE in aqueous solution, whereas Cu-salophen/CNT only achieved a -2.22 mA·cm-2 current density and 57.9% FECO under the same reaction conditions. These distinct catalytic performances resulted from the different coordination activation abilities of CO2 on various metal centers.

Sensitive detection of miRNA based on enzyme-propelled multiple photoinduced electron transfer strategy.

A method is presented that uses photoinduced electron transfer (PET) for the determination of microRNAs (miRNAs) in clinical serum samples and complicated cell samples by using a smartphone. miRNA-21 is adopted as a model analyte. A 3'-phosphorylated DNA probe containing AgNCs is synthesized and hybridized with miRNA-21. Subsequently, the probe is cleaved specifically by duplex-specific nuclease to form 3'-hydroxylated products, then extended by terminal deoxynucleotidyl transferase (TdT) with superlong G for G-quadruplex/hemin units fabrication. In this way, PET occurred between AgNCs and produced G-quadruplex/hemin units, leading to the fluorescence quenching of AgNCs. Notably, the fluorescence images can be captured and translated into digital information by smartphone, resulting in a direct quantitative determination of miRNA. As a result, our strategy for miRNA assay is achieved with a satisfactory detection limit of 1.43 pM. Interestingly, TdT-propelled G-quadruplex/hemin units as multiple electron acceptors promote the sensitivity of miRNA monitoring. Different miRNAs assays are realized by adjusting the complimentary sequences of DNA probe. These qualities not only broaden the practical application of PET-based strategy, but also provide a new insight into the nucleic acid detection. Schematic representation of AgNCs and enzyme-propelled photoinduced electron transfer strategy. It has been successfully applied for detection of miRNA by image analysis software. The method displays portability and accuracy for miRNA determination, meeting the potential for biochemical and clinical applications in resource-limited settings.

A semi-dry chemistry hydrogel-based smart biosensing platform for on-site detection of metal ions.

Balancing operability and performance has long been a focus of research in bioanalysis and biosensing. In this work, between the traditional wet chemistry and dry chemistry, we develop a semi-dry smart biosensing platform with favourable operability and performance for metal ions detection. This platform is based on the integration of a stimuli-responsive hydrogel with intelligent image recognition. The hydrogel consists of agarose as a matrix and well-designed fluorescent DNA probes as response elements. Target metal ions in a test sample can diffuse into the hydrogel and activate the DNA probes, outputting fluorescence signals for intelligent imaging. In this way, sensitive and convenient detection of metal ions such as potassium ions (K+) and mercury ions (Hg2+) can be achieved without the assistance of huge instruments and professional workers. The detection limits for K+ and Hg2+ are 0.34 mM and 5.6 nM, respectively. Detection of ions in serum and lake water is also available. Moreover, the hydrogel-based biosensing platform exhibits favorable selectivity, anti-degradation ability, and long-term stability. High-throughput testing can be also achieved by punching multiple test microwells in a single piece of hydrogel. The concept and successful practice of a semi-dry chemistry-based strategy make up for the shortcomings of wet chemistry and dry chemistry, and provide a promising approach for on-site testing.

DNA Hydrogel-Based Three-Dimensional Electron Transporter and Its Application in Electrochemical Biosensing.

Electrochemical biosensing relies on electron transport on the electrode surface. However, the limited functional area of the two-dimensional electrode prevents the qualitative breakthrough in the efficiency of electron transfer. Here, a three-dimensional electron transporter was constructed to improve the efficiency of electron transfer by using an interface-immobilized DNA hydrogel. A three-dimensional pure DNA hydrogel is constructed and used as a scaffold for electron transfer. Then, an electron mediator is embedded in the DNA hydrogel through intercalative binding, and DNAzyme with intrinsic peroxidase-like activity is introduced at the node of the hydrogel scaffold to fabricate an electrochemical biosensor. The conduction of the electron mediator in the scaffold enables the acquisition of long-distance DNAzyme catalytic signals, thereby overcoming the limitation of two-dimensional electrodes. This three-dimensional electron transporter is significant for enriching the toolbox of electrochemical biosensing and can provide potential support for the development of highly sensitive biosensors.

Luminescent europium(III)-organic framework for visual and on-site detection of hydrogen peroxide via a tablet computer.

A luminescent metal-organic framework of type Eu(III)-MOF has been fabricated for visual and on-site fluorometric determination of hydrogen peroxide (H2O2) via a tablet computer. The maximum excitation and emission peaks of type Eu(III)-MOF were found at λex = 290 nm and λem = 615 nm, respectively. The average length of Eu-MOF is 1.21 ± 0.07 µm. In the presence of the target H2O2, Fe2+ is transmitted into Fe3+ via Fenton reaction, leading to a fluorescence quenching of Eu-MOF. Therefore, visible color change occurred from bright red into colorless. Interestingly, by means of tablet computer's digital camera and ImageJ software, fluorescent signals were captured and transduced into digital parameters, resulting in a linear relationship between fluorescence intensity and the concentration of H2O2. As a result, the determination of H2O2 without the aid of complicated instruments is achieved in the range 2.0 µM to 0.2 mM with a detection limit of 1.02 µM. Our approach has been successfully applied to quantify H2O2 in serum, urine, and waste water with good recovery and precision (< 2.5% RSD). Besides, our assay has been exploited for visual detection of H2O2 released from HepG2 cells with the advantages of portability and accuracy. Moreover, the strategy displays acceptable selectivity and stability. Hence, our assay provides an alternative practical method for on-site determination of H2O2 without the need for instruments. Graphical abstract Schematic representation of the synthesis procedure of a luminescent Eu-MOF, which has been successfully applied for on-site detection of H2O2 via Fenton reaction and imaging analysis technique. The method exhibits handheld and accuracy for H2O2 determination, holding the potential for biochemical and clinical applications in remote regions.

Transferrin Receptor Targeted Cellular Delivery of Doxorubicin Via a Reduction-Responsive Peptide-Drug Conjugate.

PURPOSE: Transferrin receptors (TfRs) are overexpressed in tumor cells but are scarce in normal tissues, which makes TfR an attractive target for drug treatment of cancer. The objective of this study was to evaluate the potential of BP9a (CAHLHNRS) as a peptide vector for constructing TfR targeted peptide-drug conjugates and selective drug delivery. METHODS: Doxorubicin (DOX) was connected to BP9a via a disulfide-intercalating linker to afford a reduction-responsive BP9a-SS-DOX conjugate. By using HepG2 human liver cancer cells and L-O2 normal hepatic cells as TfR over-expressing and low-expressing in vitro models, respectively, TfR mediated cellular uptake of this conjugate was studied by using flow cytometry and confocal laser scanning microscopy. The in vitro cytotoxicities of the conjugate against HepG2 and L-O2 cells were examined by cell counting kit-8 (CCK-8) assay to evaluate its tumorous specificity. RESULTS: Cellular uptake and TfR blockage test results showed that the BP9a-SS-DOX conjugate gained entry into HepG2 cells via endocytosis mediated by TfR and mainly accumulated in cytoplasm. The in vitro antiproliferative activity of this conjugate against HepG2 cells (IC50 6.21 ± 1.12 µM) was approximately one-sixth of that of free DOX (IC50 1.03 ± 0.13 µM). However, its cytotoxic effect on L-O2 cells was obviously reduced compared with that of free DOX. CONCLUSIONS: The BP9a-SS-DOX conjugate showed specific antiproliferative activity against HepG2 liver cancer cells. Our study suggests that BP9a has the potential to target chemotherapeutic agents to tumor cells over-expressing TfR and facilitate selective drug delivery.

Synthesis, in vitro stability, and antiproliferative effect of d-cysteine modified GnRH-doxorubicin conjugates.

Overexpression of gonadotropin-releasing hormone (GnRH) receptor in many tumors but not in normal tissues makes it possible to use GnRH analogs as targeting peptides for selective delivery of cytotoxic agents, which may help to enhance the uptake of anticancer drugs by cancer cells and reduce toxicity to normal cells. The GnRH analogs [d-Cys6 , desGly10 , Pro9 -NH2 ]-GnRH, [d-Cys6 , desGly10 , Pro9 -NHEt]-GnRH, and [d-Cys6 , α-aza-Gly10 -NH2 ]-GnRH were conjugated with doxorubicin (Dox), respectively, through N-succinimidyl-3-maleimidopropionate as a linker to afford three new GnRH-Dox conjugates. The metabolic stability of these conjugates in human serum was determined by RP-HPLC. The antiproliferative activity of the conjugates was examined in GnRH receptor-positive MCF-7 human breast cancer cell line by MTT assay. The three GnRH-Dox conjugates showed improved metabolic stability in human serum in comparison with AN-152. The antiproliferative effect of conjugate II ([d-Cys6 , desGly10 , Pro9 -NHEt]-GnRH-Dox) on MCF-7 cells was higher than that of conjugate I ([d-Cys6 , desGly10 , Pro9 -NH2 ]-GnRH-Dox) and conjugate III ([d-Cys6 , α-aza-Gly10 -NH2 ]-GnRH-Dox), and the cytotoxicity of conjugate II against GnRH receptor-negative 3T3 mouse embryo fibroblast cells was decreased in comparison with free Dox. GnRH receptor inhibition test suggested that the antiproliferative activity of conjugate II might be due to the cellular uptake mediated by the targeting binding of [d-Cys6 -des-Gly10 -Pro9 -NHEt]-GnRH to GnRH receptors. Our study indicates that targeting delivery of conjugate II mediated by [d-Cys6 -des-Gly10 -Pro9 -NHEt]-GnRH is a promising strategy for chemotherapy of tumors that overexpress GnRH receptors.

Surface-immobilized and self-shaped DNA hydrogels and their application in biosensing.

Hydrogels are of great interest in the field of biosensing for their good biocompatibility, plasticity, and capability of providing 3D scaffolds. Nevertheless, the application of hydrogels has not been linked with broad surface biosensing systems yet. To overcome the limitations, here for the first time, surface-immobilized pure DNA hydrogels were synthesized using a surficial primer-induced strategy and adopted for biosensing applications. The DNA hydrogel 3D scaffold is successfully constructed on a transparent ITO electrode, which facilitates both colourimetric and electrochemical measurements. Results show that the hydrogel is able to wrap enzymes solidly and exhibits favourable stability under different conditions. Owing to the free diffusion of the micromolecular targets throughout the hydrogel, while isolating the enzymes from the macromolecular interferences outside the hydrogel, the direct colourimetric and electrochemical detection of hydrogen peroxide and bilirubin in serum is achieved. The detection limit of hydrogen peroxide in serum is 22 nM by colourimetric analysis and 13 nM by electrochemical measurement. The detection limit of bilirubin is 32 nM, a favourable limit that could be used in jaundice diagnosis. In addition, the enzyme@hydrogel can be easily regenerated and the catalytic activity is retained for a few cycles, thus allowing the recycling of the hydrogel-based biosensing system. The successful integration of DNA hydrogels with surface biosensing systems will greatly expand the applications of hydrogels for diagnostic and environmental monitoring purposes.

Design of DNA nanostructure-based interfacial probes for the electrochemical detection of nucleic acids directly in whole blood.

Here we report a robust and sensitive DNA nanostructure-based electrochemical (E-nanoDNA) sensor that utilizes tetrahedral DNA nanostructures (TDNs) as an interfacial probe to detect biomolecules in a single-step procedure. In this study, we have firstly demonstrated that the use of TDNs can significantly suppress electrochemical background signals compared to traditional linear DNA probes upon introduction of base mismatches in the edges of TDNs. After further optimization of the two functional strands in the TDNs, quantitative, one-step detection of DNA can be achieved in the picomolar range in less than 10 min, and directly in complex media. Moreover, the baseline drift of this biosensor can be greatly decreased even after several hours in flowing whole blood in vitro, which suggests that the sensor holds potential to be employed in live animals. Furthermore, through replacing functional strands with aptamers or other DNA elements, this E-nanoDNA sensor can be easily used to probe various analytes, broadening the application range of the proposed sensor.

Embedding Capture-Magneto-Catalytic Activity into a Nanocatalyst for the Determination of Lipid Kinase.

The use of emerging nanocatalysts to investigate the activity of biocatalysts (protein enzymes, catalytic RNAs, etc.) is increasingly receiving attention from material, analytic, and biomedical scientists. Here, we have first fabricated a three-in-one nanocatalyst, the nitrilotriacetic acid (NTA)-modified magnetite nanoparticle (NTA-MNP), to develop an integrated magneto-colorimetric (MagColor) assay for lipid kinase activity so as to solve the inherent problems in a lipid kinase assay. On the basis of three integrated functions of the NTA-MNPs (capture, magnetic separation, and peroxidase activity), the catalytic activity of lipid kinase is directly converted to colorimetric signals. Therefore, the assay procedure is significantly simplified such that in one step the visual detection of lipid kinase activity is possible. Moreover, the whole system responds sensitively in the case that NTA-MNPs recognize a few numbers of the reaction sites, which efficiently initiates the chromogenic reaction of a large amount of chromogens; thus, the detection limit decreases to 6.5 ± 5.8 fM, about three orders of magnitude lower as compared to that of enzyme-linked immune-sorbent assay. So, by embedding desired functions into nanocatalysts, the assay for biocatalysts becomes easy, which may promisingly provide useful tools for biomedical and clinical research in the future.