Colorimetric determination of ascorbic acid using a polyallylamine-stabilized IrO2/graphene oxide nanozyme as a peroxidase mimic.

The authors describe a peroxidase-mimicking nanozyme composed of IrO2 and graphene oxide (GO). It was synthesized from monodisperse IrO2 nanoparticles with an average diameter of 1.7 ± 0.3 nm that were prepared by pulsed laser ablation in ethanol. The nanoparticles were then placed on polyallylamine-modified GO nanosheets through electrostatic interaction. The peroxidase-like activity of the resulting nanocomposites was evaluated by catalytic oxidation of 3,3',5,5'-tetramethylbenzidine in the presence of H2O2. Kinetic results demonstrated that the catalytic behavior of the nanocomposites follows Michaelis-Menten kinetics. Experiments performed with terephthalic acid and cytochrome C confirmed that the peroxidase-like activity originated from the electron transfer mechanism rather than from generation of hydroxy radicals. The peroxidase-like activity is inhibited in the presence of ascorbic acid (AA). Based on this property, a colorimetric assay was developed for the determination of AA by exploiting the peroxidase-like activity of IrO2/GO nanocomposites. The linear relationship between absorbance at 652 nm and the concentration of AA was acquired. The limit of detection for AA is 324 nM. Further applications of the method for AA detection in real samples were also successfully demonstrated. Graphical abstractSchematic of the preparation of polyallylamine (PAH)-stabilized IrO2/GO nanocomposites and the colorimetric detection of AA based on the peroxidase-like activity of IrO2/GO nanocomposites.

Facile synthesis of IrO2/rGO nanocomposites with high peroxidase-like activity for sensitive colorimetric detection of low weight biothiols.

In this work, we reported a novel nanozyme synthesized by decorating highly dispersed ultrafine IrO2 nanoparticles on reduced graphene oxide (rGO) nanosheets via a simple hydrothermal method. The as-prepared IrO2/rGO nanocomposites exhibited intrinsic peroxidase-like activity and could catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to produce blue product in the presence of H2O2. Catalytic kinetic of IrO2/rGO nanocomposites followed Michaelis-Menten behavior, exhibiting a higher affinity to TMB than horseradish peroxidase (HRP) enzyme. Catalytic mechanism studies suggested that the peroxidase-like activity of IrO2/rGO nanocomposites originated from their ability of electron transfer between substrate and H2O2. On the basis of high peroxidase-like activity of IrO2/rGO nanocomposites, a colorimetric strategy for rapid and sensitive detection of low weight biothiols was developed. The colorimetric detection assays for low weight biothiols showed high selectivity against other amino acids. Therefore, the IrO2/rGO nanozyme is expected for promising potential applications in the biosensor, diagnostics and environment.

Multifunctional inhibitors of ß-amyloid aggregation based on MoS2/AuNR nanocomposites with high near-infrared absorption.

Recent advances in nanotechnology have developed a lot of opportunities for biological applications. In this work, multifunctional MoS2/AuNR nanocomposites with unique high NIR absorption were designed via combining MoS2 nanosheets and gold nanorods (AuNRs). The nanocomposites were synthesized through electrostatic self-assembly and showed high stability and good biocompatibility. Then they were used to modulate the aggregation of amyloid-ß peptides, destabilize mature fibrils under NIR irradiation, and eliminate Aß-induced ROS against neurotoxicity. The inhibition and destabilization effects were confirmed by Thioflavin T (ThT) fluorescence assay and transmission electron microscopy (TEM). Cell viability assay and ROS assay revealed that MoS2/AuNR nanocomposites could alleviate Aß-induced oxidative stress and cell toxicity. More importantly, both MoS2 nanosheets and AuNRs can be used as NIR photothermal agents, MoS2/AuNR nanocomposites have enhanced ability of disrupting Aß fibrils and improved cell viability by generating local heat under low power NIR irradiation. Our results provide new insights into the design of new multifunctional systems for the treatment of amyloid-related diseases.

MoO3-x nanodots with dual enzyme mimic activities as multifunctional modulators for amyloid assembly and neurotoxicity.

Development of effective inhibitors toward Aß aggregation and reactive oxygen species (ROS) scavengers are of crucial therapeutic implications for Alzheimer's disease (AD). Herein, a novel agent with dual enzyme mimic activities has been fabricated as a multifunctional Aß fibrillation modulator. MoO3-x nanodots were synthesized by pulsed laser ablation (PLA) method in MoS2 nanosheets solutions, which may act directly as numerous fine targets. MoO3-x nanodots showed a uniform and monodispersed morphology, and the tiny dots were around 3-5 nm with a narrow size distribution. Due to the efficient charge transition between Mo5+/Mo6+ on the dots surface, MoO3-x nanodots exhibited excellent catalase and SOD mimic activities, which were adopted to alleviate Aß-mediated oxidative stress. Moreover, MoO3-x nanodots can efficiently inhibit Aß aggregation and destabilize the preformed fibrils, and eventually protect neuronal cells from apoptosis induced by Aß. Taken together, MoO3-x nanodots with multifunctional roles can act as a potential therapeutic strategy for treatment of amyloid induced neurotoxicity.

Controllable fabrication of magnetic core-shell nanocomposites with high peroxide mimetic properties for bacterial detection and antibacterial applications.

Pathogenic bacterial infection has become a growing threat to public health; therefore, exploration of a sensitive and specific method for the identification of bacteria is very important. In this report, we fabricated a new magnetic core-shell nanocomposite with a homogenous morphology. The Fe3O4 nanoparticle core with a diameter of 15 nm was coated with a thin silica layer, and the thickness of the layer was finely adjusted to about 10 nm. Pt nanoclusters with a diameter of 2-3 nm were anchored uniformly on the surface to form Fe3O4@SiO2-Pt nanocomposites. These nanocomposites exhibited excellent peroxide enzyme activity and acted as a signal-output probe for the identification of pathogenic bacteria. This strategy was also based on using vancomycin (Van) as the capture agent in an ELISA procedure. The detection limit for S. aureus was around 1 × 101 cfu mL-1. Furthermore, Fe3O4@Si-Pt nanocomposites also show ideal bacteria separation and inhibition effects, and can act as a multifunctional platform for bacterial detection and antibacterial applications.

Quercetin nanoparticles with enhanced bioavailability as multifunctional agents toward amyloid induced neurotoxicity.

Quercetin (Que), as one of the most potent flavonoids, has gained appreciable attention in anti-fibrosis, anti-oxidation and other therapeutic research due to its numerous pharmacological and biological functions. However, low aqueous solubility, poor permeability and instability in physiological media have limited its widespread application in the pharmaceutical field. Herein, a facile method for fabrication of Que nanoparticles (NPs) has been developed by pulsed laser ablation (PLA). Que NPs exhibited homogeneous morphology with an average diameter of 50 nm and narrow distributions, which revealed enhanced solubility and drug release activity. Owing to the advance of NPs in modulating the amyloid fibrillation process as well as the anti-oxidative ability, Que NPs were applied to regulate Aß42 assembly and they showed multifunctional effects: inhibiting Aß aggregation, destabilizing Aß fibrils, decreasing Aß-induced oxidative stress and Aß-mediated cytotoxicity. Thus, Que NPs with enhanced bioavailability may act as a multifunctional therapeutic agent toward amyloid-related diseases.

GO-AgCl/Ag nanocomposites with enhanced visible light-driven catalytic properties for antibacterial and biofilm-disrupting applications.

Nanomaterials with visible light-driven photocatalytic activity have attracted much attention due to their excellent abilities in degradation of various organic pollutants as well as inactivating bacteria. Herein, graphene oxide (GO) enwrapped silver chloride/silver (AgCl/Ag) nanocomposites with high visible light absorption were designed and fabricated as efficient antibacterial agents. AgCl NPs were synthesized in the presence of GO first and Ag NPs were coated on AgCl surface by heat reduction to form GO-AgCl/Ag nanocomposites. The as prepared nanocomposites revealed improved stability, higher absorption properties in the visible light region. The enhanced antibacterial activity was observed by quantification of colony forming units (CFU) and morphological changes of bacteria. The antibacterial mechanism of GO-AgCl/Ag was also investigated by evaluating membrane permeability and ROS level. Moreover, GO-AgCl/Ag composites can eliminate bacterial biofilms more efficiently under visible light irradiation. Our results provide new insights into the design of new multifunctional systems for antibacterial applications.

Graphene oxide-iron oxide nanocomposite as an inhibitor of Aß 42 amyloid peptide aggregation.

Inhibiting amyloid ß (Aß) aggregation has drawn much attention because it is one of the main reasons for the cause of Alzheimer's disease (AD). Here we have synthesized a nanocomposite of graphene oxide-iron oxide (GOIO) and demonstrated its ability of modulating Aß aggregation. The inhibition effects of the GOIO nanocomposite on Aß aggregates was studied by Thioflavin T fluorescence assay, circular dichroism and transmission electron microscopy, respectively. Furthermore, the cell viability study revealed that the GOIO nanocomposite can reduce the toxicity of Aß fibrils to neuroblastoma cells. Our results demonstrated that the combination of GO and IO as a nanocomposite material has a potential use for the design new therapeutic agents for the treatment of Alzheimer's disease.

Molybdenum Disulfide Nanoparticles as Multifunctional Inhibitors against Alzheimer's Disease.

The complex pathogenic mechanisms of Alzheimer's disease (AD) include the aggregation of ß-amyloid peptides (Aß) into oligomers or fibrils as well as Aß-mediated oxidative stress, which require comprehensive treatment. Therefore, the inhibition of Aß aggregation and free-radical scavenging are essential for the treatment of AD. Nanoparticles (NPs) have been found to influence Aß aggregation process in vitro. Herein, we report the inhibition effects of molybdenum disulfide (MoS2) NPs on Aß aggregation. Polyvinylpyrrolidone-functionalized MoS2 NPs were fabricated by a pulsed laser ablation method. We find that MoS2 NPs exhibit multifunctional effects on Aß peptides: inhibiting Aß aggregation, destabilizing Aß fibrils, alleviating Aß-induced oxidative stress, as well as Aß-mediated cell toxicity. Moreover, we show that MoS2 NPs can block the formation of the Ca2+ channel induced by Aß fibrils in the cell membrane for the first time. Thus, these observations suggest that MoS2 NPs have great potential for a multifunctional therapeutic agent against amyloid-related diseases.

Excellent peroxidase mimicking property of CuO/Pt nanocomposites and their application as an ascorbic acid sensor.

Due to low cost and high stability, the applications of inorganic nanomaterials as efficient alternatives to natural enzymes are drawing much attention. In this work, novel CuO/Pt nanocomposites with high peroxidase-like activity were designed and applied for the colorimetric detection of ascorbic acid (AA). The nanocomposites were prepared by decorating Pt NPs on the surface of CuO nanosheets, which displayed good uniformity and showed improved distribution and stability. The catalytic activity of the prepared CuO/Pt nanocomposites was tested against various chromogenic substrates in the presence of H2O2, which displayed efficient peroxidase-like activity and high catalytic stability against temperature. The catalytic mechanism of the CuO/Pt nanocomposites was investigated by hydroxyl radical detection. The peroxidase-like activity decreased significantly in the presence of AA. On the basis of the inhibition property, a colorimetric biosensor was constructed by using the CuO/Pt nanocomposites for the detection of AA. It showed a high selectivity against amino acids, carbohydrates and normal ions. Thus, this work provides new insights into the application of inorganic nanocomposite-based nanozymes in the biosensing field.

CpG loaded MoS2 nanosheets as multifunctional agents for photothermal enhanced cancer immunotherapy.

Single or few-layered MoS2 nanosheets, as a novel class of 2D nanomaterials, have received tremendous attention due to their fantastic physical and chemical properties. Here, we fabricated MoS2-PEG-CpG with a small and uniform size as a multifunctional platform for photothermal enhanced immunotherapy. MoS2 nanosheets were fabricated by chemical exfoliation and further probe sonication. To realize MoS2-based adjuvant delivery, MoS2 nanosheets were functionalized with cytosine-phosphate-guanine (CpG) and polyethylene glycol (PEG) to form MoS2-PEG-CpG nanoconjugates. As an efficient nanocarrier with excellent near infrared-light (NIR) absorbing performance, MoS2-PEG-CpG significantly promotes CpG intracellular accumulation and the effect can be further enhanced by photothermal treatment. In addition, the enhanced uptake can stimulate the production of proinflammatory cytokines and remarkably elevate the immune response level. Finally, we found that MoS2-PEG-CpG could reduce the proliferative activity of cancer cells when co-cultured with a macrophage-like cell upon NIR irradiation, implying a novel strategy for multifunctional therapeutics against cancers.

Synergistic Inhibitory Effect of Peptide-Organic Coassemblies on Amyloid Aggregation.

Inhibition of amyloid aggregation is important for developing potential therapeutic strategies of amyloid-related diseases. Herein, we report that the inhibition effect of a pristine peptide motif (KLVFF) can be significantly improved by introducing a terminal regulatory moiety (terpyridine). The molecular-level observations by using scanning tunneling microscopy reveal stoichiometry-dependent polymorphism of the coassembly structures, which originates from the terminal interactions of peptide with organic modulator moieties and can be attributed to the secondary structures of peptides and conformations of the organic molecules. Furthermore, the polymorphism of the peptide-organic coassemblies is shown to be correlated to distinctively different inhibition effects on amyloid-ß 42 (Aß42) aggregations and cytotoxicity.

Pt74Ag26 nanoparticle-decorated ultrathin MoS2 nanosheets as novel peroxidase mimics for highly selective colorimetric detection of H2O2 and glucose.

To extend the functionalities of two-dimensional graphene-like layered compounds as versatile materials, the modification of transition metal dichalcogenide nanosheets such as MoS2 with metal nanoparticles is of great and widespread interest. However, few studies are available on the preparation of bimetallic nanoparticles supported on MoS2. Herein, a facile and efficient method to synthesize MoS2-PtAg nanohybrids by decorating ultrathin MoS2 nanosheets with octahedral Pt74Ag26 alloy nanoparticles has been reported. The as-prepared MoS2-Pt74Ag26 nanohybrids were investigated as novel peroxidase mimics to catalyze the oxidation of classical peroxidase substrate 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2, producing a blue colored reaction and exhibiting typical Michaelis-Menten kinetics. MoS2-Pt74Ag26 has a higher affinity for H2O2 than horseradish peroxidase (HRP) and a higher vmax value with TMB as the substrate than MoS2. The improved catalytic activity of hybrids for colorimetric reactions could be attributed to the synergistic effects of octahedral Pt74Ag26 nanoparticles and ultrathin MoS2 nanosheets as supports. Meanwhile, the generation of active oxygen species (˙OH) by H2O2 decomposition with MoS2-Pt74Ag26 was responsible for the oxidation of TMB. On the basis of these findings, a colorimetric method based on MoS2-Pt74Ag26 nanohybrids that is highly sensitive and selective was developed for glucose detection. Lower values of the limit of detection (LOD) were obtained, which is more sensitive than MoS2 nanosheets.

Cell-Capture and Release Platform Based on Peptide-Aptamer-Modified Nanowires.

Nanowires have attracted much attention due to their potential bioapplications, such as delivery of drugs or sensing devices. Here we report the development of a unique cell-capture and release platform based on nanowires. The combination of nanowires, surface-binding peptides, and cell-targeting aptamers leads to specific and efficient capture of cancer cells. Moreover, the binding processes are reversible, which is not only useful for downstream analysis but also for reusability of the substrate. Our work provides a new method in the design of the cell-capture and release platform, which may open up new opportunities of developing cell-separation and diagnosis systems based on cell-capture techniques.

PtCo bimetallic nanoparticles with high oxidase-like catalytic activity and their applications for magnetic-enhanced colorimetric biosensing.

A novel magnetic-enhanced colorimetric assay was constructed based on aptamer conjugated PtCo bimetallic nanoparticles (NPs) with high oxidase-like catalytic activity, high water solubility, low cell toxicity, and superparamagnetic properties. It was found that the incorporation of magnetic metal Co atoms into NPs could not only be facilitated for magnetic separation, but also resulted in the significantly improved oxidase-like catalytic activity of the nanoparticles for cancer-cell detection without the destructive H2O2. The present work demonstrates a general strategy for the design of multifunctional materials based on bimetallic nanoparticles for different applications, such as biosensors, nanocatalysts and nanomedicine.

Synergistically enhanced photocatalytic and chemotherapeutic effects of aptamer-functionalized ZnO nanoparticles towards cancer cells.

Today cancer is one of the most life-threatening diseases in the world. The conventional cancer therapies, including surgery, chemo- and radiation therapies, have some disadvantages, such as limited efficiency and significant side effects. It is necessary to develop new therapeutic treatments. Herein, we integrated the targeted photocatalytic and chemotherapy in a multifunctional drug-delivery platform. The aptamer-functionalized ZnO nanoparticles (NPs) were successfully synthesized. The anti-cancer drug was loaded in the aptamer-ZnO NP system. In vitro cell cytotoxicity experiments showed that combined therapy had a higher rate of death of cancer cells compared to that of single photocatalytic or chemotherapy. Furthermore, aptamer-functionalization could greatly increase the accumulation of nanoparticles within cancer cells and lead to better therapeutic effects. The results suggest that aptamer-functionalized semiconductor nanoparticles may have potential in the development of targeted photocatalytic and chemotherapy against cancer.

Aptamer-conjugated graphene oxide-gold nanocomposites for targeted chemo-photothermal therapy of cancer cells.

The current cancer therapies in clinical practice demonstrate the need for improvements such as improving the efficiency and reducing the severe side effects. Herein, we integrated the targeted chemotherapy and photothermal therapy in a multifunctional drug-delivery platform. The targeting DNA aptamer (Apt)-modified graphene oxide-gold nanoparticle (GO-AuNP) composites were successfully synthesized. The doxorubicin (DOX)-loaded GO-AuNP-Apt system showed heat-stimulative and sustained release characteristics. In vitro cell cytotoxicity experiments showed that combined therapy had the highest rate of death of tumor cells compared to that of single photothermal therapy or chemotherapy. Furthermore, aptamer-modification could significantly enhance the accumulation of nanocomposites within cancer cells. Our study demonstrates that aptamer-modified GO-Au nanocomposites may have potential in the development of targeted photothermal therapy and chemotherapy against cancer cells.

Enhanced cell growth on nanotextured GaN surface treated by UV illumination and fibronectin adsorption.

Semiconductors are important materials used for the development of high-performance biomedical devices. Gallium nitride (GaN) is a well-known III-nitride semiconductor with excellent optoelectronic properties as well as high chemical stability and biocompatibility. The formation of tight interfaces between GaN substrates and cells would be crucial for GaN-based devices used for probing and manipulating biological processes of cells. Here we report a strategy to greatly enhance cell adhesion and survival on nanotextured GaN surface which was treated by UV illumination and fibronectin (FN) adsorption. Cell studies showed that the UV/FN treatment greatly enhanced cell adhesion and growth on nanotextured GaN surfaces. These observations suggest new opportunities for novel nanotextured GaN-based biomedical devices.

Molecular tethering effect of C-terminus of amyloid peptide aß42.

Amyloid peptides are considered to be the main contributor for the membrane disruption related to the pathogenesis of degenerative diseases. The variation of amino acids at the carboxylic terminus of amyloid peptide has revealed significant effects on the modulation of abnormal assemblies of amyloid peptides. In this work, molecular binding agents were tethered to the C-terminus of ß-amyloid peptide 1-42 (Aß42). The molecular interaction between Aß42 and molecule tethers was identified at single molecule level by using scanning tunneling microscopy (STM). The mechanistic insight into the feature variation of the self-assembly of Aß42 peptide caused by molecular tethering at C-terminus was clearly revealed, which could appreciably affect the nucleation of amyloid peptide, thus reducing the membrane disruptions.

Reduced aggregation and cytotoxicity of amyloid peptides by graphene oxide/gold nanocomposites prepared by pulsed laser ablation in water.

A novel and convenient method to synthesize the nanocomposites combining graphene oxides (GO) with gold nanoparticles (AuNPs) is reported and their applications to modulate amyloid peptide aggregation are demonstrated. The nanocomposites produced by pulsed laser ablation (PLA) in water show good biocompatibility and solubility. The reduced aggregation of amyloid peptides by the nanocomposites is confirmed by Thioflavin T fluorescence and atomic force microscopy. The cell viability experiments reveals that the presence of the nanocomposites can significantly reduce the cytotoxicity of the amyloid peptides. Furthermore, the depolymerization of peptide fibrils and inhibition of their cellular cytotoxicity by GO/AuNPs is also observed. These observations suggest that the nanocomposites combining GO and AuNPs have a great potential for designing new therapeutic agents and are promising for future treatment of amyloid-related diseases.