Hybrid Nanozyme Research Articles

Evaluation of the performance of Fe3O4/MnO2@doxorubicin hybrid nanozymes on multicellular structure and their therapeutic management to limit the growth of human breast cancer cells

Doxorubicin (DOX) is the most common treatment for breast cancer, but its effectiveness is limited by drug resistance and dose variability. Evidence suggests that nanozymes can significantly improve drug penetration and effectiveness in breast cancer treatment, owing to their stable and targeted catalytic properties. However, their varied responses and concentration-dependent toxicities present challenges. After developing pH-sensitive Fe3O4/MnO2@DOX hybrid nanozymes (FMDHN) and evaluating their physicochemical and functional properties, their efficacy was investigated on MCF-7 cells using both two-dimensional and spheroid models. Our findings reveal that FMDHNs, sized 150–270 nm, inhibit MCF-7 cell growth through drug release triggered by acidity and photothermal therapy (PTT). The catalytic efficiency of FMHN in generating O2 and ·OH further enhances cancer cell suppression. Doubling the effective concentrations of FMHN and DOX by transitioning from two-dimensional to spheroid cell structures could adversely affect normal cells, while a synergistic approach combining the DOX and FMHN effectively inhibits MCF-7 cell growth at non-toxic dose. Combining FMDHN with PTT enhances this inhibition, lowering the effective dose to 1.08 μg/mL and effectively managing toxicity. The cytotoxicity mechanism in MCF-7 spheroids shows that PTT with FMDHN significantly elevates pro-inflammatory cytokines, including TNF-α, CASP9, CASP7 and CASP3. Optimizing the concentration of pH-sensitive nanozymes based on their synergistic effects can minimize side effects and maximize their breast cancer treatment potential.Graphical

Direct synthesis of small-sized platinum nanoflowers loaded on carbon supports as highly efficient and stable uricase-like nanozyme

The development of multifunctional and high-performance nanozymes via a facile strategy is especially intriguing for biomedical applications. Here, a surfactant-free simple method was used to successfully load small-sized Pt nanoflowers (PtNFs) onto reduced graphene oxide (rGO) based on single glucose. PtNF@rGO nanozyme (NM) exhibits highly excellent catalytic activity, and displays good stability and recyclability in degrading uric acid. More importantly, this robust integrated nanozyme shows strong sulfur resistance. The analysis of the structure-function relationship indicates that the small sized nanoflower structure and the interaction between PtNF and rGO in the integrated catalysts contribute to the catalytic activity and stability collectively. Interestingly, PtNF@rGO nanozymes can mimic the cascade processes of uricase/catalase to degrade both uric acid and H2O2. Furthermore, the inhibition effect of PtNF@rGO on the crystallization of urate crystals was investigated. PtNF@rGO nanozyme prolongs the nucleation induction time (from 10 to 72 h) during the crystallization of sodium urate significantly. This study reveals the significance of morphology regulation in constructing high-performance and multifunctional hybrid nanozymes, broadening the application of nanozyme in the biomedical field.

Oxygen vacancy and heterojunction co-boosted peroxidase-like activity of KV6O15/V2O5 nanoribbons for the colorimetric detection of glutathione

Due to the high costs and relative instability of natural enzymes, there is a growing interest in the strategic design of highly efficient nanozymes. In this study, a novel hybrid nanozyme consisting of KV6O15/V2O5 nanoribbons was explored using an MXene-derived potassiation-oxidation method. The KV6O15/V2O5 NRs exhibited ultrahigh peroxidase-like activity in the oxidation of 3,3′,5,5′-tetramethylbenzidine, attributed to the coexistence of oxygen vacancies and heterojunctions that facilitated the generation of ·OH radicals from H2O2 and optimized electron transfer efficiency. A colorimetric assay based on KV6O15/V2O5 nanoribbons was developed for the rapid and sensitive detection of glutathione. The assay demonstrated a linear detection range of 0.1 to 35 μM and a low detection limit of 38.8 nM. Importantly, when applied to the analysis of glutathione in human serum samples, the sensor produced satisfactory results with recoveries ranging from 90.17 % to 108.87 % and low relative standard deviations between 0.31 % and 0.64 %. To validate practicality, we constructed a visual paper sensor, affirming the utility of this assay for the sensing of glutathione.

Glutathione‑iron hybrid nanozyme-based colorimetric sensor for specific and stable detection of thiram pesticide on fruit juices

Given the potential dangers of thiram to food safety, constructing a facile sensor is significantly critical. Herein, we presented a colorimetric sensor based on glutathione‑iron hybrid (GSH-Fe) nanozyme for specific and stable detection of thiram. The GSH-Fe nanozyme exhibits good peroxidase-mimicking activity with comparable Michaelis constant (Km = 0.551 mM) to the natural enzyme. Thiram pesticides can specifically limit the catalytic activity of GSH-Fe nanozyme via surface passivation, causing the change of colorimetric signal. It is worth mentioning that the platform was used to prepare a portable hydrogel kit for rapid qualitative monitoring of thiram. Coupling with an image-processing algorithm, the colorimetric image of the hydrogel reactor is converted into the data information for accurate quantification of thiram with a detection limit of 0.3 μg mL−1. The sensing system has good selectivity and high stability, with recovery rates in fruit juice samples ranging from 92.4% to 106.9%.

Biomimetic design of mitochondria-targeted hybrid nanozymes as superoxide scavengers for myocardial ischemia reperfusion injury protection

Biomimetic design of mitochondria-targeted hybrid nanozymes as superoxide scavengers for myocardial ischemia reperfusion injury protection

Integrating Artificial DNAzymes with Natural Enzymes on 2D MOF Hybrid Nanozymes for Enhanced Treatment of Bacteria‐Infected Wounds (Small 21/2024)

Integrating Artificial DNAzymes with Natural Enzymes on 2D MOF Hybrid Nanozymes for Enhanced Treatment of Bacteria‐Infected Wounds (Small 21/2024)

The Oxidase Mimicking Activity of MnOx NPs/Co3O4 NPs Hybrid Nanozyme for Glucose Oxidation

Herein, the hybrid nanozyme MnOx NPs/Co3O4 NPs on indium tin oxide coated glass substrate (ITO) was manufactured by imparting the porous morphology with its distinct merits: its surface valence states, oxygen vacancies, large surface area, and abundant active sites. The oxidase-like activity was investigated via the catalytic oxidation of chromogenic substrate in the presence of glucose visualized by the eyes. MnOx NPs containing Mn2+ and Mn3+ have a superior ability to oxidize glucose by reducing dissolved oxygen and producing H2O2. Co3O4 NPs, in turn, reduce H2O2 with concomitant 3,3′,5,5′-tetramethylbenzidine (TMB) oxidization. Thus, the nanozyme mimics the dual roles of glucose oxidase and peroxidase. The oxidase-like activity of hybrid nanozyme for glucose was found to be higher than those of single components. The nanozyme responded to glucose with a linear range from 60 µM to 1200 μM. The acceptable performance is probably due to the facilitated access of glucose to the proximity of the sensor surface. Good reproducibility was accomplished by virtue of the meticulous construction of NPs. Without functionalization and enzyme utilization, the fabricated nanozyme holds promise as a substitute for peroxidase and oxidase for detecting glucose.

Graphene quantum dots on TiO2 nanotubes as a light-assisted peroxidase nanozyme

Hybrid nanozyme graphene quantum dots (GQDs) deposited TiO2 nanotubes (NTs) on titanium foil (Ti/TiO2 NTs-GQDs) were manufactured by bestowing the hybrid with the advantageous porous morphology, surface valence states, high surface area, and copious active sites. The peroxidase-like activity was investigated through the catalytic oxidation of chromogenic substrate 3,3′,5,5′-tetramethylbenzidine (TMB) in the presence of H2O2, which can be visualized by the eyes. TiO2 NTs and GQDs comprising oxygen-containing functional groups can oxidize TMB in the presence of H2O2 by mimicking peroxidase enzymes. The peroxidase-mimicking activity of hybrid nanozyme was significantly escalated by introducing light illumination due to the photosensitive features of the hybrid material. The peroxidase-like activity of Ti/TiO2 NTs-GQDs enabled H2O2 determination over the linear range of 7 to 250 μM, with a LOD of 2.1 µM. The satisfying peroxidase activity is possibly due to the unimpeded access of H2O2 to the catalyst’s active sites. The porous morphology provides the easy channeling of reactants and products. The periodic structure of the material also gave rise to acceptable reproducibility. Without material functionalization, the Ti/TiO2 NTs-GQDs can be a promising substitute for peroxidases for H2O2 detection.Graphical abstract

3D Cryo‐Printed Hierarchical Porous Scaffolds Harmonized with Hybrid Nanozymes for Combinatorial Mitochondrial Therapy: Enhanced Diabetic Bone Regeneration via Micromilieu Remodeling

AbstractRegeneration of bone defects in diabetic patients has always been a significant challenge in clinical treatment. The pathologic diabetic micromilieu, characterized by mitochondrial dysfunction, excessive reactive oxygen species (ROS) accumulation, cellular senescence, and chronic inflammation, compromises innate bone healing capacity. 3D cryo‐printing technology is utilized in bone tissue engineering to fabricate hierarchical porous scaffolds that promote a conducive microenvironment for cellular adhesion, migration, proliferation, and nutrient exchange. Nanozymes are used as synthetic mimics of natural enzymes to scavenge ROS, addressing the limitations of natural antioxidative enzymes. To remodel the diabetic bone regeneration micromilieu, a 3D cryo‐printed polyaryletherketone with carboxyl groups (PAEK‐COOH) and 45S5 bioactive glass (BG) hierarchical porous scaffold (PBG scaffold), harmonized with hybrid nanozymes comprising SS31‐enhanced manganese dioxide (MnO2)‐ferritin biomimetic nanozyme (MF@S nanozyme), is developed for combinatorial mitochondrial therapy. The MF@S nanozyme specifically targets mitochondria to enhance mitochondrial function, scavenge ROS accumulated in mitochondria, and suppress mitochondrial ROS (mtROS) production, and thus rejuvenate aging cells, regulate macrophage polarization, and modulate differentiation of osteoblasts and osteoclasts. This 3D cryo‐printed PBG‐MF@S hierarchical porous scaffold combines with a combinatorial mitochondrial therapy system to remodel the diabetic micromilieu and presents a promising therapeutic approach for the regeneration of bone defects in diabetes.

Versatile MOF@COF catalyzed and magnetically multivalent aptamer assisted biosensing platform for rapid and ultrasensitive dual-mode detection of multidrug-resistant bacteria

Given the frequent occurrence of multidrug-resistant bacteria (MDRB), which pose a severe threat towards public hygiene, it is important to construct facile and sensitive strategies for the detection of MDRB. We developed a fluorescent/colorimetric dual-mode biosensing platform for the analysis of MDRB by integrating the remarkable peroxidase-like activity of boric acid-decorated fluorescent framework hybrid (MOF@COF) nanozyme and enhanced bacterial affinity of DNA programmable multivalent aptamer scaffold. The efficiency and sensitivity of the proposed analysis approach were dramatically increased due to richer aptamers and high-performance MOF@COF nanozyme. Compared with commonly used single recognition methods, multivalent aptamers and bacteria-affinity boric acid groups on the nanozyme surface could identify multiple sites of MDRBs to improve site utilization for ultrasensitive biosensing. The platform realized selective detection of Acinetobacter baumannii (AB) and Pseudomonas aeruginosa (PA) in two modes with consistent results. In colorimetry and fluorescence modes, the linear ranges of AB were 102-108 and 10–108 CFU/mL with corresponding detection limits of 12 and 2 CFU/mL, and the linear ranges of PA were 102-108 and 10–108 CFU/mL with corresponding detection limits of 10 and 3 CFU/mL, respectively. More importantly, the biosensing platform could be applied for MDRB quantification in biological specimens, including human serum, cerebrospinal fluid, and urine with remarkable recoveries (96.8–105.0%) in both modes, indicating the bright prospect of the biosensing platform for MDRB determination in clinical diagnosis.

The peroxidase-like activity of Au NPs deposited inverse opal CeO2 nanozyme for rapid and sensitive H2O2 sensing

In this study, the hybrid nanozyme gold nanoparticles deposited CeO2 inverse opal photonic crystals (IOPCs) on the glass slide was fabricated by bestowing the hybrid with the beneficial porous morphology with its unique advantages: its surface valence states, high surface area, and copious active sites. The oxidase and peroxidase-mimicking activity was studied by observing the catalytic oxidation of chromogenic substrate 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) in the presence of H2O2, which can be visualized by the eyes. Au NPs and CeO2 IOPCs consisting of Ce3+ and Ce4+ can oxidize ABTS in the presence of H2O2 by mimicking peroxidase enzymes. The peroxidase-like activity of nanozyme was substantially improved by introducing light irradiation due to the photosensitive nature of the hybrid. The peroxidase-like activity of nanozyme enabled H2O2 linear detection over the range 9 to 500 μM, with a LOD of 2.7 µM. The acceptable nanozyme activity is probably owing to the easy access of H2O2 to the active sites of nanozyme. The porous architecture led to the easy channeling of reactants and products. The periodic architecture of the nanozyme also led to decent reproducibility. Without functionalization, the nanozyme can be a promising alternative to peroxidase enzymes for hydrogen peroxide measurements.

A Pt/CeO2 Hybrid Nanozyme with Stable Peroxidase Activity for the Detection of Acetylcholine

A Pt/CeO2 Hybrid Nanozyme with Stable Peroxidase Activity for the Detection of Acetylcholine

AgAu-modified quasi-MIL-53 hybrid nanozymes with triple enzyme-like activities for boosting biocatalytic disinfection

Metal-organic frameworks (MOFs) have great potential for combating pathogenic bacterial infections and are expected to become an alternative to antibiotics. However, organic linkers obstruct and saturate the inorganic nodes of MOF structures, making it challenging to utilize the applied potential of metal centers. Here, we combined controlled ligand decarboxylation with noble metal nanoparticles to rationally remodel MIL-53, resulting in a hybrid nanozyme (AgAu@QMIL-53, AAQM) with excellent multiple enzyme-like activities that both eradicate bacteria and promote diabetic wound healing. Specifically, benefitting from oxidase (OXD)-like and peroxidase (POD)-like activities, AAQM converts oxygen (O2) and hydrogen peroxide (H2O2) into superoxide anion radicals (O2−) and hydroxyl radicals (OH) to eradicate bacteria. In in vitro antibacterial experiments, AAQM exhibited favorable killing efficacy against Pseudomonas aeruginosa (P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA) (>99 %). Notably, due to its superoxide (SOD)-like activity and outstanding reactive nitrogen species (RNS) elimination capacity, AAQM can produce adequate O2 and alleviate oxidative stress in diabetic wounds. Benefiting from the rational modification of MIL-53, the synthesized hybrid nanozyme can effectively kill bacteria while alleviating oxidative stress and ultimately promote infected diabetic wound healing. Overall, this biomimetic enzyme-catalyzed strategy will bring enlightenment to the design of self-antibacterial agents for efficient disinfection and wound healing simultaneously.

A ·OH self-suppling and dual regulation hybrid nanozyme combined with photothermal therapy to eliminate biofilms and eradicate infections

Limited by local H2O2 concentration and GSH hindrance, chemodynamic therapy (CDT) has poor antibacterial efficiency, and the pro-inflammatory response caused by CDT is often ignored. Here, a hybrid nanozyme (Fe3O4-CaO2-PDA) was synthesized, which has dual regulatory functions of ·OH and GSH, there are two stages in clearing the infection: treatment and repair. In the treatment stage, stimulated by the photothermal generated by near-infrared light (NIR), it rapidly releases a large amount of ·OH and further enhances CDT by decreasing the local GSH concentration to achieve a rapid antimicrobial effect. In the repair stage, the PDA removes the local residual ·OH, prevents over-aggregation of inflammatory cells, and regulates pro-inflammatory responses. In vitro antibacterial experiments showed that the killing rates of the hybrid nanozyme against S. aureus and E. coli were 90% and 92% respectively. At the same time, the DCFH-DA fluorescence experiment showed that the ·OH concentration was significantly controlled. in vivo, due to the function of control ·OH, nanozymes show the ability to promote collagen regeneration and regulate inflammation. In summary, this study proposed a synergistic multiple antibacterial strategy and successfully constructed a PTT-enhanced multifunctional hybrid nanozyme for efficient CDT anti-infective treatment.

Pt-Se Hybrid Nanozymes with Potent Catalytic Activities to Scavenge ROS/RONS and Regulate Macrophage Polarization for Osteoarthritis Therapy.

The activation of pro-inflammatory M1-type macrophages by overexpression of reactive oxygen species (ROS) and reactive nitrogen species (RONS) in synovial membranes contributes to osteoarthritis (OA) progression and cartilage matrix degradation. Here, combing Pt and Se with potent catalytic activities, we developed a hybrid Pt-Se nanozymes as ROS and RONS scavengers to exert synergistic effects for OA therapy. As a result, Pt-Se nanozymes exhibited efficient scavenging effect on ROS and RONS levels, leading to repolarization of M1-type macrophages. Furthermore, the polarization of synovial macrophages to the M2 phenotype inhibited the expression of pro-inflammatory factors and salvaged mitochondrial function in arthritic chondrocytes. Invivo results also suggest that Pt-Se nanozymes effectively suppress the early progression of OA with an Osteoarthritis Research International Association score reduction of 68.21% and 82.66% for 4 and 8 weeks, respectively. In conclusion, this study provides a promising strategy to regulate inflammatory responses by macrophage repolarization processes for OA therapeutic.

A histidine-functionalized ROS scavenging hybrid nanozyme for therapeutic application in Parkinson's disease pathogenesis

(1) Functionalized NPs mimic the SOD1 enzyme and demonstrate robust nanozyme activity. (2) Nanozyme exhibits mitochondrial localization and maintains redox homeostasis. (3) Nanozyme inhibits Parkinson’s Disease progression through anti-apoptotic function.

Integrating Artificial DNAzymes with Natural Enzymes on 2D MOF Hybrid Nanozymes for Enhanced Treatment of Bacteria-Infected Wounds.

Removal of invasive bacteria is critical for proper wound healing. This task is challenging because these bacteria can trigger intense oxidative stress and gradually develop antibiotic resistance. Here, the use of a multienzyme-integrated nanocatalytic platform is reported for efficient bacterial clearance and mitigation of inflammatory responses, constructed by physically adsorbing natural superoxide dismutase (SOD), in situ reduction of gold nanoparticles (Au NPs), and incorporation of a DNAzyme on 2D NiCoCu metal-organic frameworks (DNAzyme/SOD/Au@NiCoCu MOFs, termed DSAM), which can adapt to infected wounds. O2 and H2O2 replenishment is achieved and alleviated the hypoxic microenvironment using the antioxidant properties of SOD. The H2O2 produced during the reaction is decomposed by peroxidase (POD)-like activity enhanced by Au NPs and DNAzyme, releasing highly toxic hydroxyl radicals (•OH) to kill the bacteria. In addition, it possesses glutathione peroxidase (GPx)-like activity, which depletes GSH and prevents •OH loss. Systematic antimicrobial tests are performed against bacteria using this multienzyme-integrated nanoplatform. A dual-mode strategy involving natural enzyme-enhanced antioxidant capacity and artificial enzyme-enhanced •OH release to develop an efficient and novel enzyme-integrated therapeutic platform is integrated.

Metal-organic framework-modulated Fe3O4 composite au nanoparticles for antibacterial wound healing via synergistic peroxidase-like nanozymatic catalysis

Bacterial wound infections are a serious threat due to the emergence of antibiotic resistance. Herein, we report an innovative hybrid nanozyme independent of antibiotics for antimicrobial wound healing. The hybrid nanozymes are fabricated from ultra-small Au NPs via in-situ growth on metal-organic framework (MOF)-stabilised Fe3O4 NPs (Fe3O4@MOF@Au NPs, FMA NPs). The fabricated hybrid nanozymes displayed synergistic peroxidase (POD)-like activities. It showed a remarkable level of hydroxyl radicals (·OH) in the presence of a low dose of H2O2 (0.97 mM). Further, the hybrid FMA nanozymes exhibited excellent biocompatibility and favourable antibacterial effects against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. The animal experiments indicated that the hybrid nanozymes promoted wound repair with adequate biosafety. Thus, the well-designed hybrid nanozymes represent a potential strategy for healing bacterial wound infections, without any toxic side effects, suggesting possible applications in antimicrobial therapy.

Gold mineralized “hybrid nanozyme bomb” for NIR-II triggered tumor effective permeation and cocktail therapy

Lung cancer is one of the most common malignant tumors with the fastest increase in the incidence rate and mortality. Even after maximum tumor resection assistance with a radiotherapy and chemotherapy combination, the recurrence of non-small cell lung cancer is still inevitable. In addition, low targeting efficiency and poor permeability of drug delivery systems strongly affect the therapeutic efficiency of anti-cancer drugs on non-small cell lung cancer. Here we designed a gemcitabine (GEM) loaded arginine-glycine-aspartic acid-cysteine (RGDc)-modified gold mineralization “hybrid nanozyme bomb” (RGTG) to overcome those obstacles. RGDc modification improved the active targeting of liposomes to the tumor tissues with the second near-infrared (NIR-II)-triggered gold-shell disruption and GEM release. The collapsed gold-shell particles with a smaller size could penetrate the tumor solid barrier and act as photothermal therapy (PTT) agents to improve PTT therapy and starvation therapy via generating gluconic acid and reactive oxygen species (ROS). Moreover, the resting reversal effect of gold particles on tumor fibroblasts can achieve accelerating tumor penetration of gold particles and GEM. Compared to monotherapy, RGTG showed significant improvement in tumor inhibition, with a tumor volume reduction of 83% compared to the control group, which provides a promising tumor treatment platform for non-small cell lung cancer (NSCLC).

Aptamer and DNAzyme-Functionalized Cu-MOF Hybrid Nanozymes for the Monitoring and Management of Bacteria-Infected Wounds.

Metal-organic frameworks (MOFs) with peroxidase (POD)-like activity have great potential for combating drug-resistant bacterial infections. However, the use of POD-like activities is severely limited by low oxygen levels and high levels of glutathione (GSH) within the microenvironment of bacterial infection. Herein, G-quadruplex/hemin DNAzyme-aptamer probes and tannic acid-chelated Au nanoparticle (Au-TA)-decorated Cu-based MOF nanosheets (termed GATC) with triple-enzyme activities were developed for visual detection and efficient antibacterial therapy. First, the monometallic MOFs (Cu-ZIF) showed the best catalytic and loading capacity performance compared with the bimetallic MOFs (CoCu-ZIF and ZnCu-ZIF). Then, Cu-MOFs, Au-TA, and DNAzyme improve the POD-like activity to generate more hydroxyl radicals (•OH) to kill bacteria. GATC can bind to bacteria through aptamer recognition, increasing the bacterial surface contact area for efficient antibacterial activity. GATC can decompose H2O2 into O2 to alleviate hypoxia and improve the microenvironment due to its catalase (CAT)-like activity. In addition, GATC exhibited GSH peroxidase-like activity, which can avoid the loss of •OH and result in bacterial death more easily. Compared with previous studies, GATC exhibited extraordinary bactericidal ability at an extremely low dosage of 3 μg/mL against methicillin-resistant Staphylococcus aureus (MRSA). Notably, the GATC-catalyzed chromogenic reaction could accurately monitor the MRSA infection treatment process. Overall, this work could establish a therapeutic platform for the monitoring and management of bacteria-infected wounds.