Polymer coated cerium oxide nanoparticles as oxidoreductase-like catalysts

Cerium oxide nanoparticles have been shown to mimic oxidoreductase enzymes by catalyzing the decomposition of organic substrates and reactive oxygen species. This mimicry can be found in superoxide radicals and hydrogen peroxides, harmful molecules produced in oxidative stress asso-ciated diseases. Despite the fact that nanoparticle functionalization is mandatory in the context of nanomedicine, the influence of polymer coatings on their enzyme-like catalytic activity is poorly understood. In this work, six polymer coated cerium oxide nanoparticles are prepared by associa-tion of 7.8 nm cerium oxide cores with two poly(sodium acrylate) and four poly(ethylene glycol) (PEG) grafted copolymers with different terminal or anchoring end groups, such as phosphonic acids. The superoxide dismutase-, catalase-, peroxidase- and oxidase-like catalytic activities of the coated nanoparticles were systematically studied. It is shown that the polymer coatings do not af-fect the superoxide dismutase-like, impair the catalase-like and oxidase-like and surprisingly im-proves peroxidase-like catalytic activities of cerium oxide nanoparticles. It is also demonstrated that the particles coated with the PEG-grafted copolymers perform better than the poly(acrylic acid) coated ones as oxidoreductase-like enzymes, a result that confirms the benefit of having phosphon-ic acids as anchoring groups at the particle surface.Comment: 23 pages, 8 figures, 3 table

Nanoceria Inhibit the Development and Promote the Regression of Pathologic Retinal Neovascularization in the Vldlr Knockout Mouse

Many neurodegenerative diseases are known to occur and progress because of oxidative stress, the presence of reactive oxygen species (ROS) in excess of the cellular defensive capabilities. Age related macular degeneration (AMD), diabetic retinopathy (DR) and inherited retinal degeneration share oxidative stress as a common node upstream of the blinding effects of these diseases. Knockout of the Vldlr gene results in a mouse that develops intraretinal and subretinal neovascular lesions within the first month of age and is an excellent model for a form of AMD called retinal angiomatous proliferation (RAP). Cerium oxide nanoparticles (nanoceria) catalytically scavenge ROS by mimicking the activities of superoxide dismutase and catalase. A single intravitreal injection of nanoceria into the Vldlr-/- eye was shown to inhibit: the rise in ROS in the Vldlr-/- retina, increases in vascular endothelial growth factor (VEGF) in the photoreceptor layer, and the formation of intraretinal and subretinal neovascular lesions. Of more therapeutic interest, injection of nanoceria into older mice (postnatal day 28) resulted in the regression of existing vascular lesions indicating that the pathologic neovessels require the continual production of excessive ROS. Our data demonstrate the unique ability of nanoceria to prevent downstream effects of oxidative stress in vivo and support their therapeutic potential for treatment of neurodegenerative diseases such as AMD and DR

Hierarchical Assembly Of Inorganic Nanostructure Building Blocks To Octahedral Superstructures - A True Template-Free Self-Assembly

A room temperature, template-free, wet chemical synthesis of ceria nanoparticles and their long term ageing characteristics are reported. High resolution transmission electron microscopy and UV-visible spectroscopy techniques are used to observe the variation in size, structure and oxidation state, respectively as a function of time. The morphology variation and the hierarchical assembly (octahedral superstructure) of nanostructures are imputed to the inherent structural aspects of cerium oxide. It is hypothesized that the 3-5 nm individual building blocks will undergo an intra-agglomerate re-orientation to attain the low energy configuration. This communication also emphasizes the need for long term ageing studies of nanomaterials in various solvents for multiple functionalities. © IOP Publishing Ltd

Pegylated Inorganic Nanoparticles

Application of inorganic nanoparticles in diagnosis and therapy has become a critical component in the targeted treatment of diseases. The surface modification of inorganic oxides is important for providing diversity in size, shape, solubility, long-term stability, and attachment of selective functional groups. This Minireview describes the role of polyethylene glycol (PEG) in the surface modification of oxides and focuses on their biomedical applications. Such a PEGylation of surfaces provides stealth characteristics to nanomaterials otherwise identified as foreign materials by human body. The role of PEG as structure-directing agent in synthesis of oxides is also presented. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

ChemInform Abstract: PEGylated Inorganic Nanoparticles

Application of inorganic nanoparticles in diagnosis and therapy has become a critical component in the targeted treatment of diseases. The surface modification of inorganic oxides is important for providing diversity in size, shape, solubility, long-term stability, and attachment of selective functional groups. This Minireview describes the role of polyethylene glycol (PEG) in the surface modification of oxides and focuses on their biomedical applications. Such a PEGylation of surfaces provides stealth characteristics to nanomaterials otherwise identified as foreign materials by human body. The role of PEG as structure-directing agent in synthesis of oxides is also presented. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

The Role of Cerium Redox State in the SOD Mimetic Activity of Nanoceria

Cerium oxide nanoparticles (nanoceria) have recently been shown to protect cells against oxidative stress in both cell culture and animal models. Nanoceria has been shown to exhibit superoxide dismutase (SOD) activity using a ferricytochrome C assay, and this mimetic activity that has been postulated to be responsible for cellular protection by nanoceria. The nature of nanoceria\u27s antioxidant properties, specifically what physical characteristics make nanoceria effective at scavenging superoxide anion, is poorly understood. In this study electron paramagnetic resonance (EPR) analysis confirms the reactivity of nanoceria as an SOD mimetic. X-ray photoelectron spectroscopy (XPS) and UV-visible analyses of nanoceria treated with hydrogen peroxide demonstrate that a decrease in the Ce 3+/4+ ratio correlates directly with a loss of SOD mimetic activity. These results strongly suggest that the surface oxidation state of nanoceria plays an integral role in the SOD mimetic activity of nanoceria and that ability of nanoceria to scavenge superoxide is directly related to cerium(III) concentrations at the surface of the particle

Synthesis Dependent Core Level Binding Energy Shift In The Oxidation State Of Platinum Coated On Ceria-Titania And Its Effect On Catalytic Decomposition Of Methanol

Synergistic interaction of catalyst and support has attracted the interest of the catalytic community for several decades. The decomposition/oxidation of alcohols for the production of hydrogen as a source of fuel requires such support catalyst interaction. Recent studies have suggested the active role of oxide based supports on the catalytic ability of noble metals such as gold, platinum and palladium. Herein, we report the effect of synthesis technique on the catalytic activity of platinum coated on mixed ceria-titania support system. Wet impregnation technique followed by calcination was compared with the chemical reduction of platinum during the coating over oxide support. Methanol decomposition studied using an in-house built catalytic reactor coupled to a mass spectrometer showed that catalyst prepared by thermal reduction of platinum demonstrated better catalytic ability than the catalyst prepared by chemical reduction of platinum. Transmission electron microscopy revealed that the size of both platinum and ceria-titania particles remained unchanged, while the X-ray photoelectron spectroscopy (XPS) revealed that the oxidation state of platinum was modified by different coating procedures. A shift in the core level binding energy of the Pt 4f towards lower binding energy was observed with chemical reduction. Based on the XPS data it was found that platinum (on ceria-titania supports) in mixed oxidation state outperformed the Pt in reduced metallic state. Results from catalysis and in situ Fourier transform infra red spectroscopy are presented and discussed. © 2010 Elsevier B.V. All rights reserved

Investigation Of The Ligand-Nanoparticle Interface: A Cryogenic Approach For Preserving Surface Chemistry

Ligand-functionalized nanoparticles have replaced bare nanoparticles from most biological applications. These applications require tight control over size and stability of nanoparticles in aqueous medium. Understanding the mechanism of interaction of nanoparticle surfaces with functional groups of different organic ligands such as carboxylic acids is confounding despite the two decades of research on nanoparticles because of the inability to characterize their surfaces in their immediate environment. Often the surface interaction is understood by correlating the information available, in a piecemeal approach, from surface sensitive spectroscopic information on ligands and the bulk and surface information on nanoparticles. In present study we report the direct interaction of 5-7 nm cerium oxide nanoparticles surface with acetic acid. An in-situ XPS study was carried out by freezing the aqueous solution of nanoparticles to liquid nitrogen temperatures. Analysis of data collected concurrently from the ligands as well as functionalized frozen cerium oxide nanoparticles show that the acetic acid binds to the ceria surface in both dissociated and molecular state with equal population over the surface. The cerium oxide surface was populated predominantly with Ce4+ ions consistent with the thermal hydrolysis synthesis. DFT calculations reveal that the acetate ions bind more strongly to the cerium oxide nanoparticles as compared to the water molecules and can replace the hydration sphere of nanoparticles resulting in high acetate/acetic surface coverage. These findings reveal molecular level interaction between the nanoparticle surfaces and ligands, giving a better understanding of how materials behave in their immediate solution environment. This study also proposes a simple and elegant methodology to directly study the surface functional groups attached to nanoparticles in their immediate solution environment

Combined Cytotoxic And Anti-Invasive Properties Of Redox-Active Nanoparticles In Tumor-Stroma Interactions

Tumor-stroma interaction plays an important role in tumor progression. Myofibroblasts, pivotal for tumor progression, populate the microecosystem of reactive stroma. The formation of myofibroblasts is mediated by tumor derived transforming growth factor β1 (TGFβ1) which initiates a reactive oxygen species cell type dependent expression of alpha-smooth muscle actin, a biomarker for myofibroblastic cells. Myofibroblasts express and secrete proinvasive factors significantly increasing the invasive capacity of tumor cells via paracrine mechanisms. Although antioxidants prevent myofibroblast formation, the same antioxidants increase the aggressive behavior of the tumor cells. In this study, the question was addressed of whether redox-active polymer-coated cerium oxide nanoparticles (CNP, nanoceria) affect myofibroblast formation, cell toxicity, and tumor invasion. Herein, nanoceria downregulate both the expression of alpha-smooth muscle actin positive myofibroblastic cells and the invasion of tumor cells. Furthermore, concentrations of nanoceria being non-toxic for normal (stromal) cells show a cytotoxic effect on squamous tumor cells. The treatment with redox-active CNP may form the basis for protection of stromal cells from the dominating influence of tumor cells in tumor-stroma interaction, thus being a promising strategy for chemoprevention of tumor invasion. © 2011 Elsevier Ltd