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ACS Nano Oct 2023The abrogation of the self-adaptive redox evolution of tumors is promising for improving therapeutic outcomes. In this study, we designed a trimetallic alloy nanozyme...
The abrogation of the self-adaptive redox evolution of tumors is promising for improving therapeutic outcomes. In this study, we designed a trimetallic alloy nanozyme AuCuPt-PpIX (ACPP), which mimics up to five naturally occurring enzymes: glucose oxidase (GOD), superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and glutathione peroxidase (GPx). Facilitated by these enzyme-mimicking traits, the constructed ACPP nanozymes can not only disrupt the established redox homeostasis in tumors through a series of enzymatic cascade reactions but also achieve cyclic regeneration of the relevant enzyme substrates. Density functional theory (DFT) calculations have theoretically explained the synergistic effect of multimetallic doping and the possible mechanism of enzymatic catalysis. The doped Cu and Pt sites are conducive to the adsorption, activation, and dissociation of reactant molecules, whereas the Au sites are conducive to desorption, which significantly improves catalytic efficiency via a synergistic effect. Additionally, ACPP nanozymes can improve the effect of protoporphyrin (PpIX)-enabled sonodynamic therapy (SDT) by alleviating hypoxia and initiating ferroptosis by inducing lipid peroxidation (LPO) and inhibiting GPX4 activity, thus achieving multimodal synergistic therapy. This study presents a typical paradigm to enable the use of multimetallic alloy nanozymes for the treatment of tumor cells with self-adaptive properties.
Topics: Humans; Neoplasms; Peroxidase; Peroxidases; Oxidation-Reduction; Glucose Oxidase; Catalysis
PubMed: 37811650
DOI: 10.1021/acsnano.3c06833 -
Rheumatology (Oxford, England) Jul 2023Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of life-threatening autoimmune diseases. Inhibitors of apoptosis proteins (IAPs) are a...
OBJECTIVES
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of life-threatening autoimmune diseases. Inhibitors of apoptosis proteins (IAPs) are a class of molecules engaged in cell death and inflammation, interventions of which are proven effective in a number of inflammatory diseases. Here we tested whether targeting IAPs could ameliorate AAV and explored the potential mechanism.
METHODS
We collected 19 kidney specimens from patients with myeloperoxidase (MPO)-AAV to investigate the expression of IAPs. The IAP pan-inhibitor SM164 was used to treat the experimental autoimmune vasculitis (EAV) rat model of AAV. RNA sequencing of renal cortex and enrichment analysis were developed to interpret gene expression. Functional experiments were performed to investigate the role of SM164 on neutrophils and endothelial cells.
RESULTS
The expression of three IAPs (cIAP1, cIAP2 and XIAP) was upregulated in kidneys of AAV patients compared with normal controls. SM164 dramatically reduced renal injury in EAV rats. Transcriptomic analysis revealed prominent alterations in fatty acid oxidation and respiratory burst following SM164 treatment. Functional studies demonstrated that SM164 inhibited neutrophil activation induced by MPO-ANCA positive IgG or serum from MPO-AAV patients, and such inhibitory effect was abolished by gene silencing or pharmacological inhibition of fatty acid oxidation. SM164 also inhibited the adhesion of neutrophils to endothelial cells with little effect on the endothelial injury induced by serum from MPO-AAV patients.
CONCLUSION
Inhibition of IAPs with SM164 played a protective role in AAV through enhancing intracellular fatty acid oxidation in neutrophils.
Topics: Rats; Animals; Antibodies, Antineutrophil Cytoplasmic; Peroxidase; Endothelial Cells; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Neutrophils; Inhibitor of Apoptosis Proteins; Fatty Acids
PubMed: 36308438
DOI: 10.1093/rheumatology/keac621 -
Advanced Healthcare Materials Sep 2023Nanoenzymes have been widely explored for chemodynamic therapy (CDT) in cancer treatment. However, poor catalytic efficiency of nanoenzymes, especially in the tumor...
Nanoenzymes have been widely explored for chemodynamic therapy (CDT) in cancer treatment. However, poor catalytic efficiency of nanoenzymes, especially in the tumor microenvironment with insufficient H O and mild acidity, limits the effect of CDT. Herein, a new ultrathin RuCu nanosheet (NS) based nanoenzyme which has a large specific surface area and abundant channels and defects is developed. The RuCu NSs show superb catalytic efficiency for the oxidation of peroxidase substrate H O at a wide range of pH and their catalytic efficiency (k /K = 177.2 m s ) is about 14.9 times higher than that of the single-atom catalyst FeN P. Besides being an efficient nanozyme as peroxidase, the RuCu NSs possess other two enzyme activities, not only disproportionating superoxide anion to produce H O but also consuming glutathione to keep a high concentration of H O in the tumor microenvironment for Fenton reaction. With these advantages, the RuCu NSs exhibit good performance to kill cancer cells and inhibit tumor growth in mice, demonstrating a promising potential as new CDT reagent.
Topics: Animals; Mice; Peroxidase; Peroxidases; Catalysis; Glutathione; Superoxides; Tumor Microenvironment; Hydrogen Peroxide; Cell Line, Tumor; Neoplasms
PubMed: 37053081
DOI: 10.1002/adhm.202300490 -
New Biotechnology Nov 2023Lignin is the second most abundant natural polymer next to cellulose and by far the largest renewable source of aromatic compounds on the planet. Dye-decolourising... (Review)
Review
Lignin is the second most abundant natural polymer next to cellulose and by far the largest renewable source of aromatic compounds on the planet. Dye-decolourising peroxidases (DyPs) are biocatalysts with immense potential in lignocellulose biorefineries to valorize emerging lignin building blocks for environmentally friendly chemicals and materials. This work investigates the catalytic potential of the engineered PpDyP variant 6E10 for the oxidation of 24 syringyl, guaiacyl and hydroxybenzene lignin-phenolic derivatives. Variant 6E10 exhibited up to 100-fold higher oxidation rates at pH 8 for all the tested phenolic substrates compared to the wild-type enzyme and other acidic DyPs described in the literature. The main products of reactions were dimeric isomers with molecular weights of (2 × MW - 2 H). Their structure depends on the substitution pattern of the aromatic ring of substrates, i.e., of the coupling possibilities of the primarily formed radicals upon enzymatic oxidation. Among the dimers identified were syringaresinol, divanillin and diapocynin, important sources of structural scaffolds exploitable in medicinal chemistry, food additives and polymers.
Topics: Peroxidase; Lignin; Oxidoreductases; Peroxidases; Oxidation-Reduction; Phenols
PubMed: 36563877
DOI: 10.1016/j.nbt.2022.12.003 -
Molecules (Basel, Switzerland) Nov 2023Gold nanoparticles (AuNPs) can be described as nanozymes, species that are able to mimic the catalytic activities of several enzymes, such as oxidase/peroxidase,...
Gold nanoparticles (AuNPs) can be described as nanozymes, species that are able to mimic the catalytic activities of several enzymes, such as oxidase/peroxidase, reductase, or catalase. Most studies in the literature focus on the colloidal suspension of AuNPs, and it is obvious that their immobilization could open the doors to new applications thanks to their increased stability in this state. This work aimed to investigate the behavior of surfaces covered by immobilized AuNPs (iAuNPs). Citrate-stabilized AuNPs (AuNPs-cit) were synthesized and immobilized on glass slides using a simple dip coating method. The resulting iAuNPs were characterized (surface plasmon resonance, microscopy, quantification of immobilized AuNPs), and their multi-enzymatic-like activities (oxidase-, peroxidase-, and catalase-like activity) were evaluated. The comparison of their activities versus AuNPs-cit highlighted their added value, especially the preservation of their activity in some reaction media, and their ease of reuse. The huge potential of iAuNPs for heterogeneous catalysis was then applied to the degradation of two model molecules of hospital pollutants: metronidazole and methylene blue.
Topics: Catalase; Gold; Metal Nanoparticles; Peroxidase; Peroxidases
PubMed: 38005280
DOI: 10.3390/molecules28227558 -
Spectrochimica Acta. Part A, Molecular... Dec 2023The accurate surveillance and sensitive detection of deferoxamine mesylate (DFO) is of great significance to ensure the safety of thalassemia major patients. Herein, we...
The accurate surveillance and sensitive detection of deferoxamine mesylate (DFO) is of great significance to ensure the safety of thalassemia major patients. Herein, we report a new nanozyme-based colorimetric sensor platform for DFO detection. First, a metal-organic framework (ZIF-67) was used as a precursor for the synthesis of FeNiCo-LDH (Layered Double Hydroxide, LDH) via an ion exchange reaction stirring at room temperature. The results of electron microscopy and nitrogen adsorption-desorption showed that FeNiCo-LDH exhibited a 3D hollow and mesopores structure, which supplied more exposed active sites and faster transfer of mass. The as-prepared FeNiCo-LDH showed superior peroxidase-like activity with a low K and high υ. It can catalyze the decomposition of HO to generate reactive oxygen species (ROS) and further react with 3,3',5,5'-tetramethylbenzidine (TMB) to form blue oxidized TMB (oxTMB), which has a characteristic absorption at 652 nm. Once DFO was introduced, it can complex with FeNiCo-LDH and inhibit the peroxidase-like activity of FeNiCo-LDH, making the color of oxTMB lighter. The quantitative range of DFO was 0.8-28 μM with a detection limit of 0.71 μM. This established method was applied to the detection of DFO content in urine samples of thalassemia patients, and the spiked recoveries were falling between 97.7% and 109.6%, with a relative standard deviation was less than 5%, providing a promising tool for the clinical medication of thalassemia patients.
Topics: Humans; Deferoxamine; Colorimetry; Hydrogen Peroxide; Catalysis; Peroxidases; Peroxidase
PubMed: 37506456
DOI: 10.1016/j.saa.2023.123156 -
International Journal of Molecular... Nov 2023Aphids are a serious threat to rapeseed ( L.) production, and cause unmanageable loss. Therefore, effective prevention and management strategies are urgently required to...
Aphids are a serious threat to rapeseed ( L.) production, and cause unmanageable loss. Therefore, effective prevention and management strategies are urgently required to avoid losses. AK-12 isolated from a dead aphid with aphicidal activity was tagged with a green fluorescent protein through a natural transformation. The transformed strains were checked for stability and growth, and the best-performing strain was tested for its colonization inside and outside the rapeseed plant. The stability of AK-12-GFP reached more than 95%, and the growth curve was consistent with that of AK-12. After 30 days of treatment, the colonization of 1 × 10 CFU/g was recorded in rapeseed leaves. Interestingly, AK-12 reduced the aphid transmission rate compared with the control and improved the growth of the rapeseed seedlings. Meanwhile, the AK-12 strain also exhibited phosphorus, potassium-solubilizing, and nitrogen-fixing activity, and produced 2.61 µg/mL of IAA at 24 h. Regulation in the activity of four enzymes was detected after the AK-12 treatment. Phenylalanine ammonia lyase (PAL) was recorded at a maximum of 86.84 U/g after 36 h, and catalase (CAT) decreased after 48 h; however, peroxidase (POD) and polyphenol oxidase (PPO) reached the maximum within 12 h of AK-12 application. Additionally, important resistance genes related to these enzymes were upregulated, indicating the activation of a defense response in the rapeseed against aphids. In conclusion, defense enzymes and defense-related gene activation could improve the pest resistance in rapeseed, which has good application prospects for the future to be developed into biopesticide.
Topics: Animals; Brassica napus; Aphids; Bacillus amyloliquefaciens; Brassica rapa; Peroxidase
PubMed: 37958876
DOI: 10.3390/ijms242115893 -
Talanta Aug 2024The development of nanomaterials with multi-enzyme-like activity is crucial for addressing challenges in multi-enzyme-based biosensing systems, including cross-talk...
The development of nanomaterials with multi-enzyme-like activity is crucial for addressing challenges in multi-enzyme-based biosensing systems, including cross-talk between different enzymes and the complexities and costs associated with detection. In this study, Pt nanoparticles (Pt NPs) were successfully supported on a Zr-based metal-organic framework (MOF-808) to create a composite catalyst named MOF-808/Pt NPs. This composite catalyst effectively mimics the functions of acetylcholinesterase (AChE) and peroxidase (POD). Leveraging this capability, we replaced AChE and POD with MOF-808/Pt NPs and constructed a biosensor for sensitive detection of acetylcholine (ACh). The MOF-808/Pt NPs catalyze the hydrolysis of ACh, resulting in the production of acetic acid. The subsequent reduction in pH value further enhances the POD-like activity of the MOFs, enabling signal amplification through the oxidation of a colorimetric substrate. This biosensor capitalizes on pH variations during the reaction to modulate the different enzyme-like activities of the MOFs, simplifying the detection process and eliminating cross-talk between different enzymes. The developed biosensor holds great promise for clinical diagnostic analysis and offers significant application value in the field.
Topics: Metal-Organic Frameworks; Biosensing Techniques; Acetylcholine; Acetylcholinesterase; Platinum; Metal Nanoparticles; Hydrogen-Ion Concentration; Zirconium; Biomimetic Materials; Peroxidase; Colorimetry; Catalysis; Limit of Detection
PubMed: 38677169
DOI: 10.1016/j.talanta.2024.126112 -
Advanced Healthcare Materials Nov 2023Metal ion-facilitated chemodynamic therapy (CDT) is an emerging method for treating cancer. However, its potential is hindered by its low catalytic performance in weakly...
Metal ion-facilitated chemodynamic therapy (CDT) is an emerging method for treating cancer. However, its potential is hindered by its low catalytic performance in weakly acidic tumor microenvironments (TMEs) and the severe toxicity of free metal ions. A new approach to tumor therapy, chemodynamic vascular disruption (CVD), is introduced using metal-free, peroxidase (POD)-mimetic multihydroxylated [70] fullerene (MHF) nanocatalysts. The research shows that MHF contains C···O active sites, as demonstrated by density functional theory (DFT) calculations, and converts H O into ∙OH across a pH range of 6.0-10.0. The generation of ∙OH and the dismantling of tumor blood vessels are observed in real-time using mouse dorsal skin-fold chamber (DSFC) models. Applying proteomics, it is discovered that the CVD mechanism involves the nanocatalytic MHF enhancing H O decomposition in the TME, producing ∙OH. This damages tumor vascular endothelial junction proteins, causing vascular leakage and subsequently cutting off the vascular supply to the tumor cells. This method deviates from the traditional CDT that targets tumor cells. Instead, the proficient MHF nanocatalysts aim to directly disrupt the tumor vasculature, enhancing anti-tumor efficiency without triggering harmful toxicity. The proposed CVD therapeutic strategy enhances the application of gentle carbon nanocatalysts in cancer therapy, offering new perspectives on nanocatalytic medicine.
Topics: Animals; Mice; Peroxidase; Peroxidases; Endothelium, Vascular; Neoplasms; Disease Models, Animal; Cardiovascular Diseases; Cell Line, Tumor; Hydrogen Peroxide; Tumor Microenvironment
PubMed: 37506058
DOI: 10.1002/adhm.202301306 -
Scientific Reports Jul 2023Drought tolerance is a complex trait in plants that involves different biochemical mechanisms. During two years of study (2019-2020), the responses of 64 arugula...
Drought tolerance is a complex trait in plants that involves different biochemical mechanisms. During two years of study (2019-2020), the responses of 64 arugula genotypes to drought stress were evaluated in a randomized complete block design with three replications under field conditions. Several metabolic traits were evaluated, i.e. relative water content, photosynthetic pigments (chlorophyll and carotenoids), proline, malondialdehyde, enzymatic antioxidants (catalase, ascorbate peroxidase, and peroxidase), total phenolic and flavonoid contents and seed yield. On average, the drought stress significantly increased the proline content (24%), catalase (42%), peroxidase (60%) and malondialdehyde activities (116%) over the two years of study. As a result of the drought stress, the seed yield (18%), relative water content (19.5%) and amount of photosynthetic pigments (chlorophyll and carotenoids) dropped significantly. However, the total phenolic and flavonoid contents showed no significant changes. Under drought stress, the highest seed yields were seen in the G, G, G, G and G genotypes, while the lowest value was observed in the G genotype (94 g plant). According to the findings, when compared to the drought-sensitive genotypes, the drought-tolerant arugula genotypes were marked with higher levels of proline accumulation and antioxidant enzyme activity. Correlation analysis indicated the positive effects of peroxidase, catalase and proline on seed yield under drought conditions. These traits can be considered for the selection of drought-tolerant genotypes in breeding programs.
Topics: Antioxidants; Carotenoids; Catalase; Chlorophyll; Coloring Agents; Droughts; Flavonoids; Malondialdehyde; Peroxidase; Peroxidases; Plant Breeding; Seeds; Brassicaceae; Acclimatization
PubMed: 37429927
DOI: 10.1038/s41598-023-38028-6