Critical Comparison of the Superoxide Dismutase-like Activity of Carbon Antioxidant Nanozymes by Direct Superoxide Consumption Kinetic Measurements

Wu, Gang; Berka, Vladimír; Derry, Paul J.; Mendoza, Kimberly; Kakadiaris, Eugenia; Roy, Trenton; Kent, Thomas A.; Tour, James M.; Tsai, Ah‐Lim

doi:10.1021/acsnano.9b04229

Cited by 47 publications

(54 citation statements)

References 46 publications

(116 reference statements)

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“…ROS refers to the reduction products of oxygen in the body, including oxygen radicals (e.g., O 2 · − , · OH, HO 2 · ) and certain nonradical oxidizing agents (e.g., ozone, H 2 O 2 , hypochlorous acid) [ 206 ]. SOD is selected as a favorable tool to anti-oxidation and anti-aging since it could transform superoxide anion radicals into H 2 O 2 and O 2 [ 207 ]. Numerous nanomaterials have been proven as SOD mimics, such as Mn 3 O 4 [ 208 ], Au[ 63 ], MnO 2 [ 209 ], and CeO 2 [ 210 ].…”

Section: Properties Of Metal- and Metal Oxide-based Nanozymesmentioning

confidence: 99%

A Review on Metal- and Metal Oxide-Based Nanozymes: Properties, Mechanisms, and Applications

et al. 2021

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Since the ferromagnetic (Fe3O4) nanoparticles were firstly reported to exert enzyme-like activity in 2007, extensive research progress in nanozymes has been made with deep investigation of diverse nanozymes and rapid development of related nanotechnologies. As promising alternatives for natural enzymes, nanozymes have broadened the way toward clinical medicine, food safety, environmental monitoring, and chemical production. The past decade has witnessed the rapid development of metal- and metal oxide-based nanozymes owing to their remarkable physicochemical properties in parallel with low cost, high stability, and easy storage. It is widely known that the deep study of catalytic activities and mechanism sheds significant influence on the applications of nanozymes. This review digs into the characteristics and intrinsic properties of metal- and metal oxide-based nanozymes, especially emphasizing their catalytic mechanism and recent applications in biological analysis, relieving inflammation, antibacterial, and cancer therapy. We also conclude the present challenges and provide insights into the future research of nanozymes constituted of metal and metal oxide nanomaterials.

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Section: Properties Of Metal- and Metal Oxide-based Nanozymesmentioning

confidence: 99%

A Review on Metal- and Metal Oxide-Based Nanozymes: Properties, Mechanisms, and Applications

et al. 2021

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“…The SOD activity of different carboxyfullerenes was also dependent on their reduction potentials; the higher the reduction potential, the higher the SOD dismutation activity [80]. Another example is hydrophilic carbon clusters that are oxidized carbon nanoparticles with a high affinity for electrons, which react with superoxide through a two-electron process with the formation of H 2 O 2 as well as poly(ethylene glycolated) hydrophilic carbon clusters [81,82]. The authors used chemiluminescence techniques to prove that nanoparticles of fullerenols Gd@C 82 (OH) 22 and C 60 (OH) 22 , as well as malonate-adduct C 60 (C(COOH) 2 ) 2 were more efficient scavengers of SARs than water-soluble underivatized C 60 [22].…”

Section: Activity Mechanismsmentioning

confidence: 99%

Non-Functionalized Fullerenes and Endofullerenes in Aqueous Dispersions as Superoxide Scavengers

et al. 2020

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Endohedral metal fullerene are potential nanopharmaceuticals for MRI; thus, it is important to study their effect on reactive oxygen species (ROS) homeostasis. Superoxide anion radical is one of the key ROS. The reactivity of aqueous dispersions of pristine (non-functionalized) fullerenes and Gd@C82 endofullerene have been studied with respect to superoxide in the xanthine/xanthine oxidase chemiluminescence system. It was found that C60 and C70 in aqueous dispersions react with superoxide as scavengers by a similar mechanism; differences in activity are determined by cluster parameters, primarily the concentration of available, acting molecules at the surface. Gd endofullerene is characterized by a significantly (one-and-a-half to two orders of magnitude) higher reactivity with respect to C60 and C70 and is likely to exhibit nanozyme (SOD-mimic) properties, which can be accounted for by the nonuniform distribution of electron density of the fullerene cage due to the presence of the endohedral atom; however, in the cell model, Gd@C82 showed the lowest activity compared to C60 and C70, which can be accounted for by its higher affinity for the lipid phase.

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“…Over the past decade, nanozymes, nanomaterials with intrinsic enzyme-like properties have attracted significant interest for application in multiple fields owing to their advantages (i.e., high and tunable catalytic activity, low cost, easy large scale production, and high stability) over the drawbacks of natural enzymes (i.e., low stability, high cost, laborious preparation, and low recyclability) 1-3 . Since the discovery of first iron-containing nanozyme in last decade 4 , numerous nanomaterials have been elucidated to have oxidase 5 , catalase 6 , SOD 7,8 , peroxidase 9 , monooxygenase 10 , hydrolase 11 , laccase 12 mimicking activities and therefore been used in diverse applications like the destruction of biofilm, removal of algal bloom, immunoassay, tissue staining, cancer treatment, and glucose biosensing. However, despite being the most promising candidate as catalytic biomedicine, the clinical translation of nanozymes for therapeutic usage is still lacking [13][14][15] .…”

Section: Main Textmentioning

confidence: 99%

“…The exceptional selectivity of the nanozyme towards H 2 O 2 is probably due to the formation of a polar peroxido species rather than •OH radicals 9 . The peroxido species reacts further with the nucleophile (GSH cofactor) to form [8] glutathione disulfide (GSSG) (detailed in computational studies). GPx mimics often tend to show haloperoxidase activity 41 GSOH undergoes a condensation reaction with a molecule of GSH to form the GSSG 43 .…”

Section: Main Textmentioning

confidence: 99%

Incorporation of a Biocompatible Nanozyme in Cellular Antioxidant Enzyme Cascade Reverses Huntington’s Like Disorder in Preclinical Model

Adhikari

Mondal

Das

et al. 2020

Preprint

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The potentiality of nano-enzymes in therapeutic use has directed contemporary research to develop a substitute for natural enzymes, which are suffering from several disadvantages including low stability, high cost, and difficulty in storage. However, inherent toxicity, inefficiency in the physiological milieu, and incompatibility to function in cellular enzyme networks limit the therapeutic use of nanozymes in living systems. Here, we have shown that citrate functionalized manganese-based biocompatible nanoscale material (C-Mn3O4 NP) efficiently mimics glutathione peroxidase enzyme in the physiological milieu and easily incorporates into the cellular multienzyme cascade for H2O2 scavenging. A detailed computational study reveals the mechanism of the nanozyme action. We further established the in vivo therapeutic efficacy of C-Mn3O4 nanozyme in a preclinical animal model of Huntington’s disease, a prevalent progressive neurodegenerative disorder, which has no effective medication till date.SUMMARYAlthough, nano-enzymes have shown lots of promises in the management of several diseases, two major concerns limit their clinical translation. Apart from the inherent toxicity of the constituent materials (e.g., cerium, vanadium, gold, etc.), activities of contemporary nanozymes are often inhibited in physiological milieu. Furthermore, most of them are incapable of incorporation into the cellular metabolic networks for functioning in tandem and parallel with natural enzymes, a major criteria for potential therapeutics.Here, we have shown that citrate-functionalized spherical Mn3O4 nanoparticles can efficiently mimic glutathione peroxidase (GPX) enzyme without the limitations of contemporary nanozymes, and effectively manage neurodegenerative Huntington’s disease in preclinical animal model. The choice of the material in the nanozyme lies on the fact that Mn is an essential micronutrient for mammals, and the stabilizing ligand citrate helps the nanoparticles to cross the blood-brain-barrier to reach brain. We have shown that the nanozyme can easily be incorporated in cellular antioxidant enzyme cascade. The specificity and efficacy of the nanozyme in the cascade was significantly higher compared to other reported nanozymes. We have justified our experimental findings with a detailed computational study. Understanding the mode of operation and management of Huntington’s disease in preclinical animal trial using a biocompatible (non-toxic) nanozyme as a part of the metabolic network may uncover a new paradigm in nanozyme based therapeutic strategy.

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Critical Comparison of the Superoxide Dismutase-like Activity of Carbon Antioxidant Nanozymes by Direct Superoxide Consumption Kinetic Measurements

Cited by 47 publications

References 46 publications

A Review on Metal- and Metal Oxide-Based Nanozymes: Properties, Mechanisms, and Applications

A Review on Metal- and Metal Oxide-Based Nanozymes: Properties, Mechanisms, and Applications

Non-Functionalized Fullerenes and Endofullerenes in Aqueous Dispersions as Superoxide Scavengers

Incorporation of a Biocompatible Nanozyme in Cellular Antioxidant Enzyme Cascade Reverses Huntington’s Like Disorder in Preclinical Model

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