Browsing by Subject "Nanozyme"

Now showing 1 - 3 of 3
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    Ferumoxytol Nanoparticles Target Biofilms Causing Tooth Decay in the Human Mouth
    (American Chemical Society, 2021) Liu, Yuan; Huang, Yue; Kim, Dongyeop; Ren, Zhi; Oh, Min Jun; Cormode, David P.; Hara, Anderson T.; Zero, Domenick T.; Koo, Hyun; Cariology, Operative Dentistry and Dental Public Health, School of Dentistry
    Severe tooth decay has been associated with iron deficiency anemia that disproportionally burdens susceptible populations. Current modalities are insufficient in severe cases where pathogenic dental biofilms rapidly accumulate, requiring new antibiofilm approaches. Here, we show that ferumoxytol, a Food and Drug Administration-approved nanoparticle formulation for treating iron deficiency, exerts an alternative therapeutic activity via the catalytic activation of hydrogen peroxide, which targets bacterial pathogens in biofilms and suppresses tooth enamel decay in an intraoral human disease model. Data reveal the potent antimicrobial specificity of ferumoxytol iron oxide nanoparticles (FerIONP) against biofilms harboring Streptococcus mutans via preferential binding that promotes bacterial killing through in situ free-radical generation. Further analysis indicates that the targeting mechanism involves interactions of FerIONP with pathogen-specific glucan-binding proteins, which have a minimal effect on commensal streptococci. In addition, we demonstrate that FerIONP can detect pathogenic biofilms on natural teeth via a facile colorimetric reaction. Our findings provide clinical evidence and the theranostic potential of catalytic nanoparticles as a targeted anti-infective nanomedicine.
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    Harshly Oxidized Activated Charcoal Enhances Protein Persulfidation with Implications for Neurodegeneration as Exemplified by Friedreich’s Ataxia
    (MDPI, 2024-12-13) Vo, Anh T. T.; Khan, Uffaf; Liopo, Anton V.; Mouli, Karthik; Olson, Kenneth R.; McHugh, Emily A.; Tour, James M.; Manoj, Madhavan Pooparayil; Derry, Paul J.; Kent, Thomas A.; Anatomy, Cell Biology and Physiology, School of Medicine
    Harsh acid oxidation of activated charcoal transforms an insoluble carbon-rich source into water-soluble, disc structures of graphene decorated with multiple oxygen-containing functionalities. We term these pleiotropic nano-enzymes as "pleozymes". A broad redox potential spans many crucial redox reactions including the oxidation of hydrogen sulfide (H2S) to polysulfides and thiosulfate, dismutation of the superoxide radical (O2-*), and oxidation of NADH to NAD+. The oxidation of H2S is predicted to enhance protein persulfidation-the attachment of sulfur to cysteine residues. Persulfidated proteins act as redox intermediates, and persulfidation protects proteins from irreversible oxidation and ubiquitination, providing an important means of signaling. Protein persulfidation is believed to decline in several neurological disorders and aging. Importantly, and consistent with the role of persulfidation in signaling, the master antioxidant transcription factor Nrf2 is regulated by Keap1's persulfidation. Here, we demonstrate that pleozymes increased overall protein persulfidation in cells from apparently healthy individuals and from individuals with the mitochondrial protein mutation responsible for Friedreich's ataxia. We further find that pleozymes specifically enhanced Keap1 persulfidation, with subsequent increased accumulation of Nrf2 and Nrf2's antioxidant targets.
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    SOD1 Is an Integral Yet Insufficient Oxidizer of Hydrogen Sulfide in Trisomy 21 B Lymphocytes and Can Be Augmented by a Pleiotropic Carbon Nanozyme
    (MDPI, 2024-11-07) Mouli, Karthik; Liopo, Anton V.; Suva, Larry J.; Olson, Kenneth R.; McHugh, Emily A.; Tour, James M.; Derry, Paul J.; Kent, Thomas A.; Anatomy, Cell Biology and Physiology, School of Medicine
    Down syndrome (DS) is a multisystemic disorder that includes accelerated aging caused by trisomy 21. In particular, overexpression of cystathionine-β-synthase (CBS) is linked to excess intracellular hydrogen sulfide (H2S), a mitochondrial toxin at higher concentrations, which impairs cellular viability. Concurrent overexpression of superoxide dismutase 1 (SOD1) may increase oxidative stress by generating excess hydrogen peroxide (H2O2) while also mitigating the toxic H2S burden via a non-canonical sulfide-oxidizing mechanism. We investigated the phenotypic variability in basal H2S levels in relation to DS B lymphocyte cell health and SOD1 in H2S detoxification. The H2S levels were negatively correlated with the DS B lymphocyte growth rates but not with CBS protein. Pharmacological inhibition of SOD1 using LCS-1 significantly increased the H2S levels to a greater extent in DS cells while also decreasing the polysulfide products of H2S oxidation. However, DS cells exhibited elevated H2O2 and lipid peroxidation, representing potential toxic consequences of SOD1 overexpression. Treatment of DS cells with a pleiotropic carbon nanozyme (pleozymes) decreased the total oxidative stress and reduced the levels of the H2S-generating enzymes CBS and 3-mercaptopyruvate sulfurtransferase (MPST). Our results indicate that pleozymes may bridge the protective and deleterious effects of DS SOD1 overexpression on H2S metabolism and oxidative stress, respectively, with cytoprotective benefits.