Multifunctional Nanozyme Research Articles

Application of Multifunctional Nanozymes in Tumor Therapy.

Tumors are one of the main diseases threatening human life and health. The emergence of nanotechnology in recent years has introduced a novel therapeutic avenue for addressing tumors. Through the amalgamation of nanotechnology's inherent attributes with those of natural enzymes, nanozymes have demonstrated the ability to initiate catalytic reactions, modulate the biological microenvironment, and facilitate the adoption of multifaceted therapeutic approaches, thereby exhibiting considerable promise in the realm of cancer treatment. In this Review, the application of nanozymes in chemodynamic therapy, radiotherapy, photodynamic therapy, photothermal therapy, and starvation therapy are summarized. Moreover, a detailed discussion regarding the mechanism of conferring physiotherapeutic functionality upon catalytic nanosystems is provided. It is posited that this innovative catalytic treatment holds significant potential to play a crucial role within the domain of nanomedicine.

Engineered nanozymes for speedy colorimetric biosensing and sensitive cascaded-catalytic determining of norfloxacin

Nanozymes based on default engineering have garnered considerable interest for their ability to effectively imitate natural enzyme catalysis settings for detection. With the widespread use of quinolone antibiotics, it is worth noting that the antibiotic drugs represented by norfloxacin (NOR) are concentration-dependent when used. Therefore, residual or dosage differences in the body can lead to some central toxicity hazards, so monitoring and detection are necessary. Herein, we reported Fe3O4@MIL-101@polypyrroles (PPys) nanozymes with default engineering, which possessed a porous core–shell structure with Fe3O4 as the core and MIL-101 and PPys as the shells in sequence. X-Ray photoelectron spectroscopy (XPS) analysis and density functional theory (DFT) calculation were to guide and analyze the catalytic pathway of peroxidase-like activity. Furthermore, a versatile intelligent colorimetric and sensing platform has been established to achieve sensitive cascaded-catalytic determining norfloxacin (NOR). In addition, NOR has a lower threshold of acceptability detection of 0.14 μM, which is better than the interpreted detection methods. We have firstly explored the detection mechanisms of ascorbate (H2A) and NOR and discovered that NOR could selectively oxidize Fe2+ and support Bi-Bi mechanisms in the process of H2O2 catalysis. Excellent guidelines for the design of multifunctional nanozyme catalysts were provided by the inquiry.

Integrating Bimetallic Nanoparticles with Covalent Organic Frameworks as Multifunctional Nanozyme for Colorimetric Detection of Hydrogen Peroxide and Glutathione

Integrating Bimetallic Nanoparticles with Covalent Organic Frameworks as Multifunctional Nanozyme for Colorimetric Detection of Hydrogen Peroxide and Glutathione

Smartphone-assisted hydrogel platform based on BSA-CeO2 nanoclusters for dual-mode determination of acetylcholinesterase and organophosphorus pesticides.

Adual-mode sensor was developed for detecting acetylcholinesterase (AChE) and organophosphorus pesticides (OPs) via bifunctional BSA-CeO2 nanoclusters (NCs) with oxidase-mimetic activity and fluorescence property. The dual-mode sensor has the characteristics of self-calibration and self-verification, meeting the needs of different detection conditions and provide more accurate results. The colorimetric sensor and fluorescence sensor have been successfully used for detecting AChE with limit of detection (LOD) of 0.081mU/mL and 0.056mU/mL, respectively, while the LOD forOPs were 0.9ng/mL and 0.78ng/mL, respectively. The recovery of AChE was 93.9-107.2% and ofOPs was 95.8-105.0% in actual samples. A novel strategy was developed to monitor pesticide residues and detect AChE level, which will motivate future work to explore the potential applications of multifunctional nanozymes.

Iron-Doped Polymer Dots with Enhanced Fluorescence and Dual Enzyme Activity for Versatile Bioassays.

Nanozymes with multiple functionalities endow biochemical sensing with more sensitive and efficient analytical performance by widening the sensing modes. Meanwhile, the target-oriented design of multifunctional nanozymes for certain biosensing remains challenging. Herein, a constructive strategy of doping iron into polymer dots (PDs) to achieve nanozymes with excellent oxidase-mimicking and peroxidase-mimicking activity is proposed. Compared with the Fe-free PDs prepared under the same mild condition, the Fe-doped PDs (Fe-PDs) exhibit greatly boosted fluorescence at 500 nm. While applying 3,3',5,5'-tetramethylbenzidine (TMB) as a chromogenic substrate, the fluorescence of the Fe-PDs can be further quenched by oxTMB due to the inner filter effect (IFE). Inspired by this, a simple but efficient colorimetric and fluorometric dual-mode sensing platform is developed for monitoring the reducing substances ascorbic acid (AA), α-glucosidase (α-Glu), and its inhibitors (AGIs). We believe that such multifunctional enzyme-mimic materials will provoke the exploration of multimode sensing strategy with strong practicality to serve as a versatile tool in biochemical sensing.

Rapid and ultra-sensitive lateral flow assay for pathogens based on multivalent aptamer and magnetic nanozyme

Ultra-sensitive LFA methods for pathogen detection commonly depended on tedious and time-consuming nucleic acid amplification. Here, a high affinity multivalent aptamer (multi-Apt) for S. aureus was obtained through exquisite engineering design. The scaffold and conformation of the multi-Apt were found to be key factors in the detection signal of aptsensors. After optimization, the binding affinity of the multi-Apt to S. aureus was improved by more than 8-fold from 135.9 nM to 16.77 nM. By the joint use of the multi-Apt and a multifunctional nanozyme Fe3O4@MOF@PtPd, a fast and ultra-sensitive LFA for S. aureus was developed (termed MA-MN LFA). In this method, a Fe3O4@MOF@PtPd nanozyme was modified with vancomycin and could efficiently capture and separate S. aureus. Moreover, the multi-Apt worked together with the nanozyme to bind with S. aureus to form a ternary complex at the same time, which simply the fabrication of LFA strip. The developed MA-MN LFA could detect S. aureus as low as 2 CFU/mL within 30 min and a wide linear range of 10–1 × 108 CFU/mL was obtained. The detection is easily operated, fast (can be completed within 30 min) and versatile for Gram-positive pathogens, thus has great potential as a powerful tool in pathogen detection.

Photothermal-enhanced multifunctional nanozyme for regulate GSH and H2O2 in tumor for improving catalytic therapy

Nanozyme-based catalytic therapy have been limited by poor catalyic performance, insufficient endogenous H2O2 concentration and high concentrations of GSH in tumor microenvironment. Herein, bimetallic MOFs were synthesized, loaded with glucose oxidase and then modified with polydopamine to obtain photothermal-enhanced nanozyme (Zr/Ce-MOFs/GOx/PDA) with GSH and H2O2 regulating properties for tumor catalytic therapy. The results showed that Zr/Ce-MOFs/GOx/PDA nanozyme exhibits intrinsic peroxidase-like and GPx-like activities , which can not only provide H2O2 in situ and decompose H2O2 into ·OH, but also eliminate GSH to protect ·OH, which can promote catalytic activities of Zr/Ce-MOFs/GOx/PDA. Besides, the Zr/Ce-MOFs/GOx/PDA with photothermal performance can further promote the catalytic activities, and the photothermal efficiency of Zr/Ce-MOFs/GOx/PDA nanozyme were 26.2%. The potential anti-tumor effect of Zr/Ce-MOFs/GOx/PDA was proved by in vitro 4T1 and in vivo 4T1-tumor-bearing mice models. It is believed that the photothermal-boosted multifunctional nanozyme-based tumor treatment strategy is a prospective method to improve therapy of tumor.

Synergistic antibacterial therapy for multidrug-resistant bacterial infections using multifunctional nanozymes

Multidrug-resistant (MDR) bacterial infections have become major threats to public health worldwide. To address this challenge, nanozyme with intrinsic enzyme-like activity has been used that can serve as broad-spectrum antibiotics. However, the efficacy of individual nanozyme is hindered by its limited catalytic activity and therapeutic efficiency. In this study, we develop broad-spectrum antibacterial nanocomposites, namely IrOx@PDA NPs-RSNO (IP NPs-RSNO), which demonstrate remarkable efficacy in eradicating MDR bacteria. The excellent antibacterial performance of IP NPs-RSNO is attributed to the synergistic effects of NIR photothermal property, NIR-enhanced peroxidase-like (POD-like) activity, and NIR-triggered release of NO. IP NPs-RSNO can effectively eliminate carbapenem-resistant Escherichia coli (CREC) and methicillin-resistant Staphylococcus aureus (MRSA), showing excellent therapeutic performance in treating MRSA-infected wounds. This work provides insights into the design of multifunctional nanozymes for antibacterial applications.

Smartphone-assisted nanozyme sensor array constructed based on reaction kinetics for the discrimination and identification of phenolic compounds

Although the research on nanozymes has attracted widespread attention in recent years, the development of highly active and multifunctional nanozymes remains a challenge. Here, a bifunctional AMP-Cu nanozyme with laccase- and catecholase-like activities was successfully prepared at room temperature with Cu2+ as the metal ion and adenosine-5′-monophosphate (AMP) as the ligand molecule.Based on the excellent catalytic performance of AMP-Cu, a three-channel colorimetric sensor array was constructed using reaction kinetics as the sensing unit to achieve high-throughput detection and identification of six common phenolic compounds at low concentrations. This strategy simplifies the construction of sensor array and demonstrates the capacity to obtain multidimensional data from a single material. Finally, with the assistance of smartphones and homemade dark boxes, a portable on-site detection method for phenolic compounds was developed. This work would contribute to the development of portable sensors and the highly efficient identification of phenolic compounds in complex samples.

An Erythrocyte-Templated Iron Single-Atom Nanozyme for Wound Healing.

Iron single-atom nanozymes represent a promising artificial enzyme with superior activity owing to uniform active sites that can precisely mimic active center of nature enzymes. However, current synthetic strategies are hard to guarantee each active site at single-atom state. In this work, an erythrocyte-templated strategy by utilizing intrinsic hemin active center of hemoglobin as sing-atom source for nanozyme formation is developed. By combining cell fixation, porous salinization, and high-temperature carbonization, erythrocytes are successfully served as uniform templates to synthesize nanozymes with fully single-atom FeN4 active sites which derived from hemin of hemoglobin, resulting in an enhanced peroxidase (POD)-like activity. Interestingly, the catalytic activity of erythrocyte-templated nanozyme (ETN) shows dependence on animal species, among which murine ETN performed superior catalytic efficiency. In addition, the as-prepared ETNs display a honeycomb-like network structure, serving as a sponge to accelerate hemostasis based on the interactions with prothrombin and fibrinogen. These features enable ETN to effectively kill methicillin-resistant Staphylococcus aureus (MRSA) by combining POD-like catalysis with near-infrared (NIR) induced photothermal effect, and subsequently suitable to promote wound healing. This study provides a proof-of-concept for facile fabrication of multifunctional nanozymes with uniform single-atom active sites by utilizing intrinsic iron structure characteristics of biogenic source like erythrocytes.

Multifunctional Nanozymes by Amplifying Intracellular Oxidative Stress for Enhanced Photothermal–Photodynamic Therapy

Multifunctional Nanozymes by Amplifying Intracellular Oxidative Stress for Enhanced Photothermal–Photodynamic Therapy

The Impressive Anti-Inflammatory Activity of Cerium Oxide Nanoparticles: More than Redox?

Cerium oxide nanoparticles (CNPs) are biocompatible nanozymes exerting multifunctional biomimetic activities, including superoxide dismutase (SOD), catalase, glutathione peroxidase, photolyase, and phosphatase. SOD- and catalase-mimesis depend on Ce3+/Ce4+ redox switch on nanoparticle surface, which allows scavenging the most noxious reactive oxygen species in a self-regenerating, energy-free manner. As oxidative stress plays pivotal roles in the pathogenesis of inflammatory disorders, CNPs have recently attracted attention as potential anti-inflammatory agents. A careful survey of the literature reveals that CNPs, alone or as constituents of implants and scaffolds, strongly contrast chronic inflammation (including neurodegenerative and autoimmune diseases, liver steatosis, gastrointestinal disorders), infections, and trauma, thereby ameliorating/restoring organ function. By general consensus, CNPs inhibit inflammation cues while boosting the pro-resolving anti-inflammatory signaling pathways. The mechanism of CNPs' anti-inflammatory effects has hardly been investigated, being rather deductively attributed to CNP-induced ROS scavenging. However, CNPs are multi-functional nanozymes that exert additional bioactivities independent from the Ce3+/Ce4+ redox switch, such as phosphatase activity, which could conceivably mediate some of the anti-inflammatory effects reported, suggesting that CNPs fight inflammation via pleiotropic actions. Since CNP anti-inflammatory activity is potentially a pharmacological breakthrough, it is important to precisely attribute the described effects to one or another of their nanozyme functions, thus achieving therapeutic credibility.

Microenvironment-Responsive Metal-Phenolic Nanozyme Release Platform with Antibacterial, ROS Scavenging, and Osteogenesis for Periodontitis.

Periodontitis is a chronic inflammatory disease deriving from dental plaque, characterized by the excessive accumulation of reactive oxygen species (ROS), matrix metalloproteinase (MMP) and other substances, resulting in the destruction of periodontal tissues. At present, the main therapeutic modalities, such as local mechanical debridement and antibiotic delivery, are not only difficult to solve the intractable bacterial biofilm effectively but also tricky to ameliorate the excessive inflammatory response as well as regenerate the impaired periodontal tissues. Herein, we have proposed the TM/BHT/CuTA hydrogel system formed by the self-assembly of the copper-based nanozyme (copper tannic acid coordination nanosheets, CuTA NSs) and the triglycerol monostearate/2,6-di-tert-butyl-4-methylphenol (TM/BHT) hydrogel. The negatively charged TM/BHT/CuTA can retain at the inflammation sites with a positive charge through electrostatic adsorption and hydrolyze in response to the increasing MMP of periodontitis, realizing the on-demand release of the CuTA nanozyme. The released CuTA nanozyme has antibacterial and antiplaque properties. Meanwhile, as a metal-phenolic nanozyme, it can scavenge multiple ROS by simulating the cascade process of superoxide dismutase (SOD) and catalase (CAT). Further, the CuTA nanozyme can modulate the macrophage polarization from M1 phenotype to M2 phenotype through the Nrf2/NF-κB pathway, which reduces the pro-inflammatory cytokines, increases the anti-inflammatory cytokines, and promotes the expression of osteogenetic genes successively, thus relieving the inflammation and accelerating the tissue regeneration of periodontitis. Altogether, this multifunctional nanozyme on-demand release platform (TM/BHT/CuTA) provides a desirable strategy for the treatment of periodontitis.

MnOx In Situ Growth-Induced Luminescence and Oxidase-Like Feature Bimodulation of CePO4:Tb Nanorods: Toward Ascorbic Acid-Related Bioanalysis in a "One-Stone-Two-Birds" Manner.

Nanozyme-based multimode detection is a useful means to improve the accuracy and stability of analytical methods. However, both multifunctional nanozymes and related multimodal sensing strategies are still very scarce. Besides, they require complex processes to fabricate and operate. To fill this gap, here we propose a spontaneous interfacial in situ growth strategy to prepare a new bifunctional material (CePO4:Tb@MnOx) featuring good oxidase-like activity and green photoluminescence for the dual-mode colorimetric/luminescence determination of ascorbic acid (AA)-related biomarkers specifically. CePO4:Tb@MnOx was gained through the controllable redox reaction between KMnO4 and CePO4:Tb nanorods. It was interestingly found that MnOx in situ growth not only significantly enhanced the enzyme-like activity but also could reversibly regulate the luminescence of CePO4:Tb via a dual quenching mechanism. More interestingly, CePO4:Tb@MnOx exhibited a distinctive response toward AA against other reducing species. A double-coordination regulation mechanism was further verified to clarify the catalytic activity and luminescence switching behaviors in CePO4:Tb@MnOx. Based on these findings, a dual-mode colorimetric/luminescence approach was established for AA sensing in a "one-stone-two-birds" manner, providing excellent selectivity, sensitivity, and practicability. Furthermore, the determination of AA-related biomarkers, including acid phosphatase activity and organophosphorus residue, was also validated by the sensing principle. Our work not only deepens the understanding of the coordinated regulation of the luminescence and enzyme-like features in lanthanide-based materials but also offers a novel way to design and develop multifunctional nanozymes for advanced bioanalytical applications.

Functional molecule-mediated assembled copper nanozymes for diabetic wound healing

BackgroundThe complex hyperglycemic, hypoxic, and reactive oxygen species microenvironment of diabetic wound leads to vascular defects and bacterial growth and current treatment options are relatively limited by their poor efficacy.ResultsHerein, a functional molecule-mediated copper ions co-assembled strategy was constructed for collaborative treatment of diabetic wounds. Firstly, a functional small molecule 2,5-dimercaptoterephthalic acid (DCA) which has symmetrical carboxyl and sulfhydryl structure, was selected for the first time to assisted co-assembly of copper ions to produce multifunctional nanozymes (Cu-DCA NZs). Secondly, the Cu-DCA NZs have excellent multicatalytic activity, and photothermal response under 808 nm irradiation. In vitro and in vivo experiments showed that it not only could efficiently inhibit bacterial growth though photothermal therapy, but also could catalyze the conversion of intracellular hydrogen peroxide to oxygen which relieves wound hypoxia and improving inflammatory accumulation. More importantly, the slow release of copper ions could accelerate cellular proliferation, migration and angiogenesis, synergistically promote the healing of diabetic wound furtherly.ConclusionsThe above results indicate that this multifunctional nanozymes Cu-DCA NZs may be a potential nanotherapeutic strategy for diabetic wound healing.

A dual-mode sensing platform based on metal–organic framework for colorimetric and ratiometric fluorescent detection of organophosphorus pesticide

Pesticide residues have raised considerable concern about environmental health and food safety. Despite a great advance in enzymatic sensors for pesticide detection, the intrinsic fragility of native enzyme and possible fake results due to single mode signal have hindered its wide application. Here, a novel dual-mode sensor is reported for organophosphorus pesticide detection by using metal–organic framework (MOF) nanozyme NH2-CuBDC as sensing element. The intrinsic peroxidase-mimicking activity and fluorescence property of NH2-CuBDC enable both colorimetric and fluorescent detection of chlorpyrifos. Compared with previously reported chlorpyrifos sensors, our sensor exhibits outstanding sensitivity, and the limits of detection (LOD, S/N = 3) in colorimetric and fluorescent modes are 1.57 ng/mL and 2.33 ng/mL, respectively. No obvious interferences from other substances were measured and chlorpyrifos analysis in real samples presented good reliability, showing practical potential. This work is anticipated to provide new insights to develop multifunctional nanozymes and integrated multi-mode sensing platforms.

Multifunctional light-controllable nanozyme enabled bimodal fluorometric/colorimetric sensing of mercury ions at ambient pH

Nanomaterials with enzyme-like catalytic features (nanozymes) find wide use in analytical sensing. Apart from catalytic characteristics, some other interesting functions coexist in the materials. How to combine these properties to design multifunctional nanozymes for new sensing strategy development is challenging. Besides, in nanozymes it is still a challenge to conveniently control the catalytic process, which also hinders their further applications in advanced biochemical analysis. To remove the above barriers, here we design a light-controllable multifunctional nanozyme, namely manganese-inserted cadmium telluride (Mn–CdTe) particles, that integrates oxidase-like activity with luminescence together, to achieve the fluorometric/colorimetric dual-mode detection of toxic mercury ions (Hg2+) at ambient pH. The Mn–CdTe exhibits a light-triggered oxidase-mimicking catalytic behavior to induce chromogenic reactions, thus enabling one to start or stop the catalytic progress easily via applying or withdrawing light irradiation. Meanwhile, the quantum dot material can exhibit bright photoluminescence, which provides the fluorometric channel to sense targets. When Hg2+ is introduced, it rapidly leans toward Mn–CdTe through electrostatic interaction and Te–Hg bonding and induces the aggregation of the latter. As a result, the luminescence of Mn–CdTe is dynamically quenched, and the masking of active sites in aggregated Mn–CdTe leads to the decrease of light-initiated oxidase-mimetic activity. According to this principle, a new fluorometric/colorimetric bimodal method was established for Hg2+ determination with excellent performance. A 3D-printed portable platform combining paper-based test strips and an App-equipped smartphone was further fabricated, making it possible to achieve in-field sensing of the analyte in various matrices.

Understanding gold nanoparticles decorated on silica as oxidase mimics and application of the light-enhanced oxidase-like activity for detection of acetylcholinesterase

Composites or hybrids have received increasing interest as new types of nanozymes that not only enhance the catalytic performance but also endow new catalytic activities. In this work, the preparation of gold nanoparticles decorated on silica (SiO2-AuNPs) exhibited both peroxidase- and oxidase-like activities, which allowed investigation of the contribution of the SiO2 support involved in the oxidase-like reaction. Specific inhibitors were used to block catalytic sites on AuNPs and verify that active sites of the peroxidase- and oxidase-like activities for SiO2-AuNPs were only located on AuNPs. Impressively. the oxidase-like activity of SiO2-AuNPs could be enhanced by visible light irradiation, which involved with superoxide anion (O2•–) as the main reactive species. In addition, the reduction of silver ions (Ag+) upon irradiation of SiO2-AuNPs supported the electron transfer between SiO2 and AuNPs. A possible mechanism for the photogenerated hot electron migration of SiO2-AuNPs was proposed. The present work provides new insights into the in-depth mechanistic understanding of SiO2 as the support and the design of composites for multi-functional nanozymes.

Cu-doped polypyrrole hydrogel with tumor catalyst activity for NIR-II thermo-radiotherapy.

Introduction: Radiotherapy (RT) is one of the key methods for treating breast cancer. However, the effect of single RT is often poor because of insufficient deposition of X-rays in tumor sites and radiation resistance induced by the abnormal tumor microenvironment (overexpression of glutathione (GSH)). The development of multifunctional RT sensitizers and synergetic therapeutic strategies is, therefore, a promising area for enhancing the anticancer effect of RT. Methods: In this study, a multifunctional nanozyme hydrogel based on Cu-doped polypyrrole (CuP) was designed to work concertedly with a second near-infrared thermal RT. The CuP-based hydrogel (CH) reached the tumor site when injected in-situ and achieved long-term storage. Results: Once stimulated with 1064-nm laser irradiation, the heated and softened hydrogel system released CuP nanozyme to provide photothermal therapy, thereby inhibiting the repair of DNA damage caused by RT. In addition, CuP with dual nanozyme activity depleted the intracellular GSH to reduce the antioxidant capacity of the tumor. Moreover, CuP converted H2O2 to produce ·OH to directly kill the tumor cells, thus enhancing the capability of low-dose RT to inhibit tumor growth. In vivo experiments showed that the CH system used in combination with a low-power 1064-nm laser and low-dose RT (4 Gy) exhibited good synergistic anticancer effects and biological safety. Discussion: As a new light-responsive hydrogel system, CH holds immense potential for radio-sensitization.

A Multifunctional Nanozyme with NADH Dehydrogenase-like Activity and Nitric Oxide Release Under Near Infrared Light Irradiation as an Efficient Therapeutic for Antimicrobial Resistance Infection and Wound Healing.

In recent years, antimicrobial resistance (AMR) has become one of the greatest threats to human health. There is an urgent need to develop new antibacterial agents to effectively treat AMR infection. Herein, a novel nanozyme platform {Cu, N-GQDs@Ru-NO} was prepared, where Cu, N-doped graphene quantum dots (Cu, N-GQDs) were covalently functionalized with a nitric oxide (NO) donor, ruthenium nitrosyl (Ru-NO). Under 808nm near infrared (NIR) light irradiation, {Cu, N-GQDs@Ru-NO} demonstrated nicotinamide adenine dinucleotide (NADH) dehydrogenase-like activity for photo-oxidizing NADH to NAD+ , thus disrupting the redox balance in bacterial cells and resulting in bacterial death; meanwhile, the onsite NIR light-delivered NO effectively eradicated the methicillin-resistant staphylococcus aureus (MRSA) bacterial and biofilms, and promoted wound healing; furthermore, the nanozyme showed excellent photothermal effect that enhanced the antibacterial efficacy as well. With the combination of NADH dehydrogenase activity, photothermal therapy, and NO gas therapy, the Cu, N-GQDs@Ru-NO nanozyme displayed both in vitro and in vivo excellent efficacy for MRSA infection and biofilm eradication, which provides a new therapeutic modality for effectively treating MRSA inflammatory wounds. This article is protected by copyright. All rights reserved.