MXene-based nanomaterials with enzyme-like properties for biomedical applications.

Recently, great progress has been made in nanozyme research due to the rapid development of nanomaterials and nanotechnology. MXene-based nanomaterials have gained considerable attention owing to their unique physicochemical properties. They have been found to have high enzyme-like properties, such as peroxidase, oxidase, catalase, and superoxide dismutase. In this mini-review, we present an overview of the recent progress in MXene-based nanozymes, with emphasis on their synthetic methods, hybridization, bio-catalytic properties, and biomedical applications. The future challenges and prospects of MXene-based nanozymes are also proposed.

Versatile gold-silver-PB nanojujubes for multi-modal detection and photo-responsive elimination against bacteria.

Bacterial infections have become a serious threat to global public health. Nanomaterials have shown promise in the development of bacterial biosensing and antibiotic-free antibacterial modalities, but single-component materials are often less functional and difficult to achieve dual bacterial detection and killing. Herein, we report a novel strategy based on the effective integration of multi-modal bacterial detection and elimination, by constructing the versatile gold-silver-Prussian blue nanojujubes (GSP NJs) via a facile template etching method. Such incorporation of multi-components involves the utilization of cores of gold nanobipyramids with strong surface-enhanced Raman scattering (SERS) activity, the shells of Prussian blue as both an efficient bio-silent SERS label and an active peroxidase-mimic, and functionalization of polyvinyl pyrrolidone and vancomycin, respectively endowing them with good colloidal dispersibility and specificity against S. aureus. The GSP NJs show operational convenience in the SERS detection and excellent peroxidase-like activity for the sensitive colorimetric detection. Meanwhile, they exhibit robust near-infrared photothermal/photodynamic effects, and the photo-promoted Ag+ ions release, ultimately achieving a high antibacterial efficiency over 99.9% in 5 min. The NJs can also effectively eliminate complex biofilms. The work provides new insights into the design of multifunctional core-shell nanostructures for the integrated bacterial detection and therapy.

IrO2 clusters loaded on dendritic mesoporous silica nanospheres with superior peroxidase-like activity for sensitive detection of acetylcholinesterase and its inhibitors.

Nanomaterials-based enzyme mimics (nanozymes), by simulating enzyme catalysis, have shown potential in numerous biocatalytic applications, but nanozymes face significant challenges of catalytic activity and reusability that may restrict their practical uses. Herein, we report facile fabrication of surface-clean IrO2 clusters supported on dendritic mesoporous silica nanospheres (DMSNs), which exhibit superior peroxidase-like activity, high thermal/long-term stability, and good recyclability. The IrO2 clusters (1.4 ± 0.2 nm in size) are obtained by the laser ablation without any ligands and possess negative surface charge, which are efficiently loaded on the amino-functionalized DMSNs by electrostatic adsorption. Owing to morphological and structural advantages, the resulted DMSN/IrO2 heterostructure displays outstanding peroxidase-like catalytic performance. Compared with horseradish peroxidase, it shows comparable affinities but higher reaction rate (2.95 × 10-7 M·s-1) towards H2O2, resulting from rapid electron transfer during the catalysis. This value is also larger than those of mesoporous silicas supported metal or metal oxides nanoparticles/clusters in the previous studies. Benefitting from excellent peroxidase-catalysis of the DMSN/IrO2, the colorimetric assays are further successfully established for the detection of acetylcholine esterase and its inhibitor, showing high sensitivity and selectivity. The work provides novel design of supported nanozymes for biosensing.

Dual ligand-induced photoelectrochemical sensing by integrating Pt/MoS2 heterostructure and Au polyhedra for sensitive detection of SARS-CoV-2.

The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with discovery of multiple mutants, has caused widespread panic and concern worldwide. The rapid antigen detection method via a single ligand recognition, although currently implemented in many countries, remains challenging for mutated antigens. Herein, we present a novel strategy using a dual recognition by two types of targeted ligands, based on photoelectrochemical (PEC) sensing for detection of SARS-CoV-2 spike protein. To demonstrate this strategy, the specific antibodies are modified onto the photoactive material with a supported nanostructure, created by loading the Pt nanoparticles onto MoS2 nanosheets (Pt/MoS2) to boost photon-to-electricity conversion efficiency. By subsequent binding of the targeted aptamers to the Au polyhedra, which act as a signal amplifier to suppress PEC photocurrent by competing with the Pt/MoS2 for the absorption of excitation light energy, the dual recognition is successfully achieved. The constructed biosensor not only shows satisfactory stability, high sensitivity, and selectivity, but is effective for test of the pseudovirus of SARS-CoV-2. The work provides useful advance for the development of PEC biosensors for sensitive detection of SARS-CoV-2.

Plasmon-enhanced photothermal properties of Au@Ti3C2Tx nanosheets for antibacterial applications.

Antibiotic-resistant bacterial strains have become an ever-increasing public concern due to their significant threats to health safety. Nanomaterial-based photothermal treatment has shown potential in antibacterial applications, but many nanomaterials exhibited limited photothermal activity that may compromise their antibacterial efficacies. Herein, we report a novel strategy based on efficient photothermal ablation and physical contact over a supported nanostructure by loading Au nanoparticles (NPs) on few-layered Ti3C2Tx nanosheets (NSs) for antibacterial treatment. Ti3C2Tx NSs are delaminated via etching and sonication, and act as a reductant for the in situ reduction of HAuCl4·xH2O, producing "naked" Au NPs without any stabilizers. Meanwhile, by adjusting the Au/Ti ratio, the size and loading of the Au NPs are finely regulated, thereby providing an ideal model of a surface-clean Au@Ti3C2Tx heterostructure for probing the composition-performance relationship. Upon irradiation with visible light, it exhibits synergistically enhanced photothermal conversion efficiency and stability, owing to the localized surface plasmonic resonance effect of Au NP and Au-NS interactions. Moreover, under visible light irradiation for 10 min, the Au@ Ti3C2Tx heterostructure exhibits excellent antibacterial activity for Gram-positive S. aureus and Gram-negative E. coli, and kills over 99% bacteria with a low dose of the nanomedicine suspension (50 µg mL-1). The work demonstrates that the incorporation of transition metal carbides with plasmonic metal nanostructures is an effective strategy to enhance the photothermal antibacterial efficacy.

Tumor-Microenvironment-Responsive Cascade Reactions by a Cobalt-Single-Atom Nanozyme for Synergistic Nanocatalytic Chemotherapy.

Nanocatalytic therapy, involving the nanozyme-triggered production of reactive oxygen species (ROS) in the tumor microenvironment (TME), has demonstrated potential in tumor therapy, but nanozymes still face challenges of activity and specificity that compromise the therapeutic efficacy. Herein, we report a strategy based on a single-atom nanozyme to initiate cascade enzymatic reactions in the TME for tumor-specific treatment. The cobalt-single-atom nanozyme, with Co-N coordination on N-doped porous carbon (Co-SAs@NC), displays catalase-like activity that decomposes cellular endogenous H2 O2 to produce O2 , and subsequent oxidase-like activity that converts O2 into cytotoxic superoxide radicals to efficiently kill tumor cells. By incorporation with doxorubicin, the therapy achieves a significantly enhanced antitumor effect in vivo. Our findings show that cascade TME-specific catalytic therapy combined with chemotherapy is a promising strategy for efficient tumor therapy.

RuO2/rGO heterostructures as mimic peroxidases for colorimetric detection of glucose.

The successful synthesis of ruthenium oxide/reduced graphene oxide (RuO2/rGO) heterostructures by one-pot hydrothermal method using graphene oxides and RuCl3 as precursors is reported. The heterostructures had high peroxidase-like (POD-like) activities, which catalyzes the oxidation of classical peroxidase substrate 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2 to create a blue colored reaction product. The catalytic activity was significantly enhanced by the synergistic effect between RuO2 nanoparticles and rGO. RuO2/rGO had a low Km of 0.068 mM and a high vmax of 1.228 × 10-7 M·s-1 towards TMB in the TMB-H2O2 catalytic oxidation system. In addition, the POD-like activity originating from the electron transfer mechanism was confirmed by cytochrome C (Cyt C) oxidation experiment. A colorimetric method based on RuO2/rGO heterostructures was developed with good sensitivity and selectivity for glucose detection with a limit of detection of 3.34 µM and a linear range of 0-1500 µM. The RuO2/rGO heterostructures have potential applications in the biomedical areas, such as biosensor and diagnostics.

Synthesis of carbon quantum dots for application of alleviating amyloid-ß mediated neurotoxicity.

Alzheimer's disease (AD) has been an intractable neurodegenerative disease among the elderly in the worldwide. One of the important pathogenic factors in AD is the aggregation of amyloid-ß 1-42 (Aß42) in AD patients' brain. Inhibition of Aß peptide aggregation is considered as one of the effective approaches against AD. Herein, a pulsed laser ablation (PLA) method is used to fabricate ultra-small carbon quantum dots (C-QDs) with uniform size. The reduced Aß42 aggregation by the C-QDs was confirmed by transmission electron microscopy (TEM), thioflavin T assay and circular dichroism (CD) spectroscopy. The results of cell viability experiments showed that the presence of the C-QDs could significantly reduce the cytotoxicity of Aß42. Furthermore, in vivo studies demonstrate that C-QDs can decrease Aß42 deposits and promote the biological activity of an AD model of Caenorhabditis elegans CL2006. This work demonstrates the viability of using ultrasmall C-QDs to inhibit amyloid-ß aggregation and alleviate amyloid-ß mediated neurotoxicity.

Intercalated Gold Nanoparticle in 2D Palladium Nanosheet Avoiding CO Poisoning for Formate Production under a Wide Potential Window.

The electrochemical CO2 reduction into formate acid over Pd-based catalysts under a wide potential window is a challenging task; CO poisoning commonly occurring on the vulnerable surface of Pd must be overcome. Herein, we designed a two-dimensional (2D) AuNP-in-PdNS electrocatalyst, in which the Au nanoparticles are intercalated in Pd nanosheets, for formate production under a wide potential window from -0.1 to -0.7 V versus a reversible hydrogen electrode. Based on the X-ray absorption spectra (XAS) characterizations, CO accumulation detection, and CO stripping voltammetry measurements, we observed that the intercalated Au nanoparticles could effectively avoid the CO formation and boost the formate production on the Pd nanosheet surface by regulating its electronic structure.

Magnet-assisted electrochemical immunosensor based on surface-clean Pd-Au nanosheets for sensitive detection of SARS-CoV-2 spike protein.

Tracking and monitoring of low concentrations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can effectively control asymptomatic transmission of current coronavirus disease 2019 (COVID-19) in the early stages of infection. Here, we highlight an electrochemical immunosensor for sensitive detection of SARS-CoV-2 antigen marker spike protein. The surface-clean Pd-Au nanosheets as a substrate for efficient sensing and signal output have been synthesized. The morphology, chemical states and excellent stable electrochemical properties of this surface-clean heterostructures have been studied. Functionalized superparamagnetic nanoparticles (MNPs) were introduced as sample separators and signal amplifiers. This biosensor was tested in phosphate buffered saline (PBS) and nasopharyngeal samples. The results showed that the sensor has a wide linear dynamic range (0.01 ng mL-1 to 1000 ng mL-1) with a low detection limit (0.0072 ng mL-1), which achieved stable and sensitive detection of the spike protein. Therefore, this immunosensing method provides a promising electrochemical measurement tool, which can furnish ideas for early screening and the reasonable optimization of detection methods of SARS-CoV-2.

Porous Au@Pt nanoparticles with superior peroxidase-like activity for colorimetric detection of spike protein of SARS-CoV-2.

The development of colorimetric assays for rapid and accurate diagnosis of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is of practical importance for point-of-care (POC) testing. Here we report the colorimetric detection of spike (S1) protein of SARS-CoV-2 based on excellent peroxidase-like activity of Au@Pt nanoparticles, with merits of rapidness, easy operation, and high sensitivity. The Au@Pt NPs were fabricated by a facile seed-mediated growth approach, in which spherical Au NPs were premade as seeds, followed by the Pt growth on Au seeds, producing uniform, monodispersed and porous Au@Pt core-shell NPs. The as-obtained Au@Pt NPs showed a remarkable enhancement in the peroxidase-mimic catalysis, which well abided by the typical Michaelis-Menten theory. The enhanced catalysis of Au@Pt NPs was ascribed to the porous nanostructure and formed electron-rich Pt shells, which enabled the catalytic pathway to switch from hydroxyl radical generation to electron transfer process. On a basis of these findings, a colorimetric assay of spike (S1) protein of SARS-CoV-2 was established, with a linear detection range of 10-100 ng mL-1 of protein concentration and a low limit of detection (LOD) of 11 ng mL-1. The work presents a novel strategy for diagnosis of COVID-19 based on metallic nanozyme-catalysis.

Two-Dimensional Nanomaterials With Enzyme-Like Properties for Biomedical Applications.

Recently, remarkable progress has been made in nanozyme research due to the rapid development of nanomaterials. Two-dimensional nanomaterials such as metal nanosheets, graphene-based materials, transition metal oxides/dichalcogenides, etc., provide enhanced physical and chemical functionality owing to their ultrathin structures, high surface-to-volume ratios, and surface charges. They have also been found to have high catalytic activities in terms of natural enzymes such as peroxidase, oxidase, catalase, and superoxide dismutase. This review provides an overview of the recent progress of nanozymes based on two-dimensional nanomaterials, with an emphasis on their synthetic strategies, hybridization, catalytic properties, and biomedical applications. Finally, the future challenges and prospects for this research are discussed.

Recent Progress of Nanozymes in the Detection of Pathogenic Microorganisms.

Infectious diseases are among the world's principal health problems. It is crucial to develop rapid, accurate and cost-effective methods for the detection of pathogenic microorganisms. Recently, considerable progress has been achieved in the field of inorganic enzyme mimics (nanozymes). Compared with natural enzymes, nanozymes have higher stability and lower cost. More interestingly, their properties can be designed for various demands. Herein, we introduce the latest research progress on the detection of pathogenic microorganisms by using various nanozymes. We also discuss the current challenges of nanozymes in biosensing and provide some strategies to overcome these barriers.

Zero-Dimensional/Two-Dimensional AuxPd100-x Nanocomposites with Enhanced Nanozyme Catalysis for Sensitive Glucose Detection.

Here, we report facile fabrication of two-dimensional (2D) Pd nanosheet (NS)-supported zero-dimensional (0D) Au nanoparticles via galvanic replacement. In the synthesis, the surface-clean Pd NSs premade not only acted as a sacrifice template for replacing Pd atoms by Au3+ ions, but served as a support substrate to support Au nanoparticles. The morphology, structure, and composition of products relied on the Au/Pd feed atomic ratio. Interestingly, the as-obtained 0D/2D AuxPd100-x (x = 4.5, 9.8, and 21) nanocomposites showed remarkably enhanced peroxidase-mimic catalysis in the model oxidation reaction, which followed the typical Michaelis-Menten theory. Compared to Pd NSs, the enhanced catalysis of AuxPd100-x was closely related to both the increased specific surface area and the modified electronic structure of Pd NSs, which resulted in a change in the catalytic pathway, that is, from hydroxyl radical generation to rapid electron transfer. The work provides a simple yet efficient avenue to build highly efficient heterogeneous catalysts based on metallic NSs, as exemplified by the superior nanozyme activity of 0D/2D bimetallic nanostructures for glucose detection.

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.

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.