Bioinspired Nanozymes as Nanodecoys for Urinary Tract Infection Treatment.

Urinary tract infections (UTIs), common bacterial infections in communities and medical facilities, are mainly mediated by FimH. The glycan sites of the uromodulin protein play a crucial role in protecting against UTIs by interacting with FimH. A bioinspired approach using glycan-FimH interactions may effectively reduce bacteria through an antiadhesive mechanism, thereby curbing bacterial resistance. However, typical antiadhesive therapy alone fails to address the excessive reactive oxygen species and inflammatory response during UTIs. To bridge this gap, antioxidant nanozymes with antiadhesive ability were developed as nanodecoys to counter bacteria and inflammation. Specifically, ultrasmall dextran-coated ceria (DEC) was engineered to address UTIs, with dextran blocking FimH adhesion and ceria exhibiting anti-inflammatory properties. DECs, metabolizable by the kidneys, reduced bacterial content in the urinary tract, mitigating inflammation and tissue damage. In murine models, DECs successfully treated acute UTIs, repeated infections, and catheter-related UTIs. This dual approach not only highlights the potential of nanozymes for UTIs but also suggests applicability to other FimH-induced infections in the lungs and bowels, marking a significant advancement in nanozyme-based clinical approaches.

Selenizing chitooligosaccharide with site-selective modification to alleviate acute liver injury in vivo.

Two selenized chitooligosaccharide (O-Se-COS and N,O-Se-COS) with different sites modification were synthesized to alleviate liver injury in vivo. Comparing to traditional COS, both selenized COS exhibited enhanced reducibility as well as antioxidant capacity in vitro. Furthermore, O-Se-COS demonstrated superior efficacy in reducing intracellular reactive oxygen species (ROS) and mitochondrial damage compared to N,O-Se-COS as its enhanced cellular uptake by the positive/negative charge interactions. Two mechanisms were proposed to explained these results: one is to enhance the enzymatic activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), which effectively scavenge free radicals; the other is to down-regulate intracellular cytochrome P450 (CYP2E1) levels, inhibiting carbon tetrachloride (CCl4)-induced peroxidation damage. In vivo studies further demonstrated the effective alleviation of CCl4-induced liver injury by selenized COS, with therapeutic efficacy observed in the following order: O-Se-COS > N,O-Se-COS > COS. Finally, hemolysis and histological tests confirmed the biosafety of both selenized COS. Taken together, these finding demonstrated that selenium has the potential to improve the biological activity of COS, and precise selenylation was more conducive to achieving the synergistic effect where 1 + 1>2.

Porous MCo2O4(M = Zn, Cu, Fe, Mn) as high efficient bi-functional catalysts for oxygen reduction and oxygen evolution reaction.

High-efficiency bi-functional electrocatalysts with long-term stability are critical to the development of many kinds of fuel cells, because that the performance of battery is limited by the slow kinetics of oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). In this work, porous MCo2O4(M = Zn, Cu, Fe, Mn) were prepared by hydrothermal method with NH4F and urea as surfactants. FeCo2O4with porous structure has more oxygen defects and the larger specific surface area than other MCo2O4(M = Zn, Cu, Mn), and it not onlysupplies more active sites but also avails the transmission of electrolyte and O2in the process of ORR and OER in 0.1 M KOH aqueous solution. Porous FeCo2O4electrode material produces less intermediate H2O2, and its ORR is mainly controlled by a 4e-reaction path. Compared with commercial Pt/C, the prepared FeCo2O4has comparable ORR activity and excellent OER activity. At the same time, the stability of FeCo2O4to ORR is significantly higher than that of commercial Pt/C. The porous FeCo2O4was prepared by facile synthesis procedure could be a potential promising bi-functional catalyst due to its high electrocatalytic activities and long-term stability for both the ORR and OER.

A Dopamine-Enabled Universal Assay for Catalase and Catalase-Like Nanozymes.

Developing a universal strategy to measure catalase (CAT)/CAT-like activity, on one hand, overcomes limitations on current assays, such as moderate sensitivity and limited sample scope; on the other hand, facilitates insightful studies on applications of CAT and CAT-like nanozymes. Herein, the oxygen-sensitive and H2O2-inhibitory self-polymerization of dopamine (DA) was demonstrated as an activity indicator of CAT or CAT-like nanozymes, which monitors the catalytically generated O2 in a hypoxic environment. A typical assay for natural CAT was achieved under the optimized conditions. Moreover, this assay was suitable for diverse types of samples, ranging from nanozymes, animal tissues, to human saliva. By comparing the merits and limitations of common methods, this assay shows all-round advantages in sensitivity, specificity, and versatility, facilitating the formulation of measurement criteria and the development of potential standardized assays for CAT (or CAT-like nanozyme) activity.

Data-informed discovery of hydrolytic nanozymes.

Nanozyme is a collection of nanomaterials with enzyme-like activity but higher environmental tolerance and long-term stability than their natural counterparts. Improving the catalytic activity and expanding the category of nanozymes are prerequisites to complement or even supersede enzymes. However, the development of hydrolytic nanozymes is still challenged by diverse hydrolytic substrates and following complicated mechanisms. Here, two strategies are informed by data to screen and predict catalytic active sites of MOF (metal-organic framework) based hydrolytic nanozymes: (1) to increase the intrinsic activity by finely tuned Lewis acidity of the metal clusters; (2) to improve the density of active sites by shortening the length of ligands. Finally, as-obtained Ce-FMA-MOF-based hydrolytic nanozyme is capable of cleaving phosphate bonds, amide bonds, glycosidic bonds, and even their mixture, biofilms. This work provides a rational methodology to design hydrolytic nanozyme, enriches the diversity of nanozymes, and potentially sheds light on future evolution of enzyme engineering.

Biochar Nanozyme from Silkworm Excrement for Scavenging Vapor-Phase Free Radicals in Cigarette Smoke.

Serious lung diseases and other health problems caused by tobacco consumption are becoming more and more prominent all over the world. Scavenging the excessive harmful free radicals in cigarette smoke is proven to be an effective method in reducing the above problems. Carbon-based nanozymes have been widely studied due to their ability of scavenging free radicals. Accordingly, the biochar derived from silkworm excrement was reported as a nanozyme with free radical scavenging ability. The biochar nanozyme calcination at 900 °C with better free radical scavenging abilities was loaded into commercial cigarette filters for the following free radical scavenging verification in tobacco smoke. Mouse model results reveal the lung tissue could be improved by the addition of biochar nanozyme. This work not only provides an effective approach to reduce the harm caused by tobacco but also provides potential applications to rationally realize low-cost, ease of production, and a wide variety of biochar sources.

Multifunctional Nanozyme Hydrogel with Mucosal Healing Activity for Single-Dose Ulcerative Colitis Therapy.

Nanozymes are nanomaterials with enzyme-like activities, which have been developed for inflammatory disease therapy by reactive oxygen species (ROS) scavenging. The application of nanozymes in ulcerative colitis (UC) treatment not only inherits the merits of small molecular antioxidants (e.g., 5-aminosalicylic acid) to scavenge ROS but also achieves catalytic recycle instead of stoichiometric consumption. However, current therapies usually ignore the repair of mucosa, the first line of defense, whose damage increases the risk of infections. Herein, a multifunctional nanozyme hydrogel is designed and verified both as an ROS scavenger and a mucosal healing enhancer for UC therapy. The chitosan-coated CeO2 nanozyme (CCNZ) not only possesses excellent ROS-scavenging ability but also exhibits satisfactory antibacterial capacity. After gelation with alginate, the optimized CCNZ1:Alg1.5 nanozyme hydrogel exhibits multiple functions, including inflamed site targeting, supporting cell growth, ROS scavenging, and antibacterial activity, which alleviates UC better than a clinical medication 5-aminosalicylic acid by even a single-dose treatment. This study reveals that a nanozyme providing mucosal healing is promising for UC therapy with excellent potential for clinical application and enriches the nanozyme research of treatment for diseases.

Structurally Engineered Light-Responsive Nanozymes for Enhanced Substrate Specificity.

Mimicking enzyme specificity via construction of on-demand geometric structures on nanozymes is of great interest in recent years. Although building substrate-specific polymers on nanozymes has achieved great success, polymer-blocked active sites would inevitably lead to decreased activity of nanozymes. Here, we have developed three photoactive metal-organic framework (MOF)-based nanozymes (called 2D-TCPP, 3D-TCPP, and AD-TCPP), which have different geometric structures as well as unshielded active sites. Together with their structural variations and excellent photoresponsive oxidase-like activities, these photoactive nanozymes exhibit structure-dependent specificity for three kinds of substrates (typical oxidase substrates, organic pollutants, and antioxidants). Moreover, AD-TCPP and 3D-TCPP show potential applications for environmental protection and bioanalysis, respectively. This work offers a promising approach to the development of nanozymes with enzyme-like specificity.

Synthesis-temperature-regulated multi-enzyme-mimicking activities of ceria nanozymes.

Ceria (CeO2) nanozymes have drawn much attention in recent years due to their unique physiochemical properties and excellent biocompatibility. It is therefore very important to establish a simple and robust guideline to regulate CeO2 with desired multi-enzyme-mimicking activities that are ideal for practical bioapplications. In this work, the multi-enzyme-mimicking activities of CeO2 were regulated in a facile manner by a wet-chemical method with different synthesis temperatures. Interestingly, a distinct response in multi-enzyme-mimicking activities of CeO2 was observed towards different synthesis temperatures. And the regulation was ascribed to the comprehensive effect of the oxygen species, size, and self-restoring abilities of CeO2. This study demonstrates that high-performance CeO2 can be rationally designed by a specific synthesis temperature, and the guidelines from radar chart analysis established here can advance the biomedical applications of ceria-based nanozymes.

Fe3O4@GO magnetic nanocomposites protect mesenchymal stem cells and promote osteogenic differentiation of rat bone marrow mesenchymal stem cells.

Fe3O4 nanoparticles (Fe3O4 NPs) are typical magnetic materials for bone tissue regeneration. However, the accompanying oxidative stress during the reaction process of Fe3O4 NPs and H2O2 in bone remodeling and disease may hinder their application. In order to reduce this side effect, we selected graphene oxide (GO) to modify Fe3O4 NPs. We showed that Fe3O4@GO magnetic nanocomposites (Fe3O4@GO MNCs) eliminated 30% of H2O2 in 3 h, and reduced the amount of ˙OH, the intermediate product of the Fenton reaction. The cellular study demonstrated that Fe3O4@GO MNCs reduced the cell damage caused by reactive oxygen species (ROS) and improved the activity of mesenchymal stem cells (MSCs). Moreover, when the magnetic field and bone morphogenetic protein-2 (BMP2) delivered by Fe3O4@GO MNCs worked together, osteogenic differentiation of MSCs in vitro was well promoted.

Surface Engineering of Biodegradable Magnesium Alloys for Enhanced Orthopedic Implants.

Magnesium (Mg) alloys have been promised for biomedical implants in orthopedic field, however, the fast corrosion rate and mode challenge their clinical application. To push Mg alloys materials into practice, a composite coating with biodegradable and high compatible components to improve anticorrosion property of an Mg alloy (i.e., AZ31) is designed and fabricated. The inner layer is micro-nano structured Mg(OH)2 through hydrothermal treatment. Then stearic acid (SA) is introduced to modify Mg(OH)2 for better reducing the gap below a surface-degradation polymer layer of poly(1,3-trimethylene carbonate). Benefited by the SA modification effect, this sandwiched coating avoids corrosive medium penetration via enhancing the adhesion strength at the interface between outer and inner layers. Both in vitro and in vivo tests indicate that the composite coating modified AZ31 perform a better anticorrosion behavior and biocompatibility compared to bare AZ31. Strikingly, a 1.7-fold improvement in volume of newly formed bone is observed surrounding the composite coating modified implant after 12 week implantation. The sandwiched biocompatible coating strategy paves a hopeful way for future translational application of Mg alloys orthopedic materials in clinics.

Light-Responsive Metal-Organic Framework as an Oxidase Mimic for Cellular Glutathione Detection.

Nanomaterials with enzyme-like characteristics (nanozymes) have been developed to mimic enzymes because of their low cost, high stability, and large-scale production. By using light as an external stimulation, one can modulate nanozymes' catalytic activities with controlled spatial and temporal precision. A few inorganic photoactive materials have been investigated to construct light-responsive oxidase-like nanozymes. However, these materials suffered from limited absorbance of visible light. To address this challenge, herein we have developed a photosensitized metal-organic framework (PSMOF) by using a derivative of Ru(bpy)32+ with stronger visible-light absorption as a PS linker. The PSMOF exhibited excellent oxidase-like activity, which could be modulated by switching light on and off. Moreover, the PSMOF was used to detect glutathione levels in both normal and cancer cells with good selectivity and high sensitivity. This study not only provides a smart strategy to modulate nanozymes' activities but also broadens the sensing applications of nanozymes.

Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes (II).

Nanozymes are nanomaterials with enzyme-like characteristics (Chem. Soc. Rev., 2013, 42, 6060-6093). They have been developed to address the limitations of natural enzymes and conventional artificial enzymes. Along with the significant advances in nanotechnology, biotechnology, catalysis science, and computational design, great progress has been achieved in the field of nanozymes since the publication of the above-mentioned comprehensive review in 2013. To highlight these achievements, this review first discusses the types of nanozymes and their representative nanomaterials, together with the corresponding catalytic mechanisms whenever available. Then, it summarizes various strategies for modulating the activity and selectivity of nanozymes. After that, the broad applications from biomedical analysis and imaging to theranostics and environmental protection are covered. Finally, the current challenges faced by nanozymes are outlined and the future directions for advancing nanozyme research are suggested. The current review can help researchers know well the current status of nanozymes and may catalyze breakthroughs in this field.

ROS scavenging Mn3O4 nanozymes for in vivo anti-inflammation.

Reactive oxygen species (ROS)-induced oxidative stress is linked to various diseases, including cardiovascular disease and cancer. Though highly efficient natural ROS scavenging enzymes have been evolved, they are sensitive to environmental conditions and hard to mass-produce. Therefore, enormous efforts have been devoted to developing artificial enzymes with ROS scavenging activities. Among them, ROS scavenging nanozymes have recently attracted great interest owing to their enhanced stability, multi-functionality, and tunable activity. It has been implicated that Mn-contained nanozymes would possess efficient ROS scavenging activities, however only a few such nanozymes have been reported. To fill this gap, herein we demonstrated that Mn3O4 nanoparticles (NPs) possessed multiple enzyme mimicking activities (i.e., superoxide dismutase and catalase mimicking activities as well as hydroxyl radical scavenging activity). The Mn3O4 nanozymes therefore significantly scavenged superoxide radical as well as hydrogen peroxide and hydroxyl radical. Moreover, they were not only more stable than the corresponding natural enzymes but also superior to CeO2 nanozymes in terms of ROS elimination. We showed that the Mn3O4 NPs not only exhibited excellent ROS removal efficacy in vitro but also effectively protected live mice from ROS-induced ear-inflammation in vivo. These results indicated that Mn3O4 nanozymes are promising therapeutic nanomedicine for treating ROS-related diseases.

Integrated nanozymes: facile preparation and biomedical applications.

Nanozymes have been viewed as the next generation of artificial enzymes due to their low cost, large specific surface area, and good robustness under extreme conditions. However, the moderate activity and limited selectivity of nanozymes have impeded their usage. To overcome these shortcomings, integrated nanozymes (INAzymes) have been developed by encapsulating two or more different biocatalysts (e.g., natural oxidases and peroxidase mimics) together within confined frameworks. On the one hand, with the assistance of natural enzymes, INAzymes are capable of specifically recognizing targets. On the other hand, nanoscale confinement brought about by integration significantly enhances the cascade reaction efficiency. In this Feature Article, we highlight the newly developed INAzymes, covering from synthetic strategies to versatile applications in biodetection and therapeutics. Moreover, it is predicted that INAzymes with superior activities, specificity, and stability will enrich the research of nanozymes and pave new ways in designing multifunctional nanozymes.

Multifunctional nanozymes: enzyme-like catalytic activity combined with magnetism and surface plasmon resonance.

Over decades, as alternatives to natural enzymes, highly-stable and low-cost artificial enzymes have been widely explored for various applications. In the field of artificial enzymes, functional nanomaterials with enzyme-like characteristics, termed as nanozymes, are currently attracting immense attention. Significant progress has been made in nanozyme research due to the exquisite control and impressive development of nanomaterials. Since nanozymes are endowed with unique properties from nanomaterials, an interesting investigation is multifunctionality, which opens up new potential applications for biomedical sensing and sustainable chemistry due to the combination of two or more distinct functions of high-performance nanozymes. To highlight the progress, in this review, we discuss two representative types of multifunctional nanozymes, including iron oxide nanomaterials with magnetic properties and metal nanomaterials with surface plasmon resonance. The applications are also covered to show the great promise of such multifunctional nanozymes. Future challenges and prospects are discussed at the end of this review.

Surfactant-free scalable synthesis of hierarchically spherical Co3O4 superstructures and their enhanced lithium-ion storage performances.

Unique hierarchically porous spherical Co(3)O(4) superstructures were synthesized via a surfactant-free hydrothermal process followed by a calcination treatment, in which the concentration of reactant cobalt (II) nitrate hexahydrate is a key factor affecting the morphology of products. X-ray powder diffraction, electron microscopies (TEM and SEM), and thermogravimetric analysis were employed to investigate the formation of Co(3)O(4) spherical superstructures. Our results suggest that they formed from numerous cubic Co(3)O(4) nanocrystals via an oriented attachment mechanism. These superstructures exhibit a high specific capacity of 1750 mA h g(-1) after the first charge-discharge cycle, and the capacity retention remains at a constant of 1600 mA h g(-1) at 0.2 C after 50 cycles. The facile, scalable, energy-efficient and environmentally friendly nature of the presented approach renders it particularly attractive from a technological standpoint. In addition, this scalable and facile synthesis method could be extended to the preparation of other transition metal oxides with specific morphologies and surface textures.

Efficient preparation of highly hydrogenated graphene and its application as a high-performance anode material for lithium ion batteries.

A novel method has been developed to prepare hydrogenated graphene (HG) via a direct synchronized reduction and hydrogenation of graphene oxide (GO) in an aqueous suspension under (60)Co gamma ray irradiation at room temperature. GO can be reduced by the aqueous electrons (e(aq)(-)) while the hydrogenation takes place due to the hydrogen radicals formed in situ under irradiation. The maximum hydrogen content of the as-prepared highly hydrogenated graphene (HHG) is found to be 5.27 wt% with H/C = 0.76. The yield of the target product is on the gram scale. The as-prepared HHG also shows high performance as an anode material for lithium ion batteries.

Self-assembly and embedding of nanoparticles by in situ reduced graphene for preparation of a 3D graphene/nanoparticle aerogel.

A 3D graphene architecture can be prepared via an in situ self-assembly of graphene prepared by a mild chemical reduction. Fe(3) O(4) nanoparticles are homogeneously dispersed into graphene oxide (GO) aqueous suspension and a 3D magnetic graphene/Fe(3) O(4) aerogel is prepared during the reduction of GO to graphene. This provides a general method to prepare 3D graphene/nanoparticle composites for a wide range of applications including catalysis and energy conversion.