In this study we have found that cerium oxide nanoparticles exhibit catalase mimetic activity. Su... more In this study we have found that cerium oxide nanoparticles exhibit catalase mimetic activity. Surprisingly, the catalase mimetic activity correlates with a reduced level of cerium in the +3 state, in contrast to the relationship between surface charge and superoxide scavenging properties.
A solution precursor plasma spray (SPPS) technique has been used for direct deposition of cerium ... more A solution precursor plasma spray (SPPS) technique has been used for direct deposition of cerium oxide nanoparticles (CNPs) from various cerium salt solutions as precursors. Solution precursors were injected into the hot zone of a plasma plume to deposit CNP coatings. A numerical study of the droplet injection model has been employed for microstructure development during SPPS. The decomposition of each precursor to cerium oxide was analyzed by thermogravimetric-differential thermal analysis and validated by thermodynamic calculations. The presence of the cerium oxide phase in the coatings was confirmed by X-ray diffraction studies. Transmission electron microscopy studies confirmed nanocrystalline (grain size <14 nm) characteristic of the coatings. X-ray photoelectron spectroscopy studies indicated the presence of a high concentration of Ce3+ (up to 0.32) in the coating prepared by SPPS. The processing and microstructure evolution of cerium oxide coatings with high nonstoichiometry are reported.
A room temperature, template-free, wet chemical synthesis of ceria nanoparticles and their long t... more 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.
Reactive oxygen and nitrogen species play a critical role in many degenerative diseases and in ag... more Reactive oxygen and nitrogen species play a critical role in many degenerative diseases and in aging. Nanomaterials, especially modified fullerenes and cerium oxide nanoparticles, have been shown to effectively protect mammalian cells against damage caused by increased reactive oxygen or nitrogen species, likely through their direct reaction with superoxide radical, since each of these materials has been shown to act as effective superoxide dismutase mimetics in vitro. This critical review discusses the chemistry of these nanomaterials and the context in which their radical scavenging activities have been studied in biological model systems. Current studies are focused on determining the uptake, metabolism, distribution, toxicity and fate of these nanomaterials in cell and animal model systems. Ultimately if shown to be safe, these nanomaterials have the potential to be used to reduce the damaging effects of radicals in biological systems (101 references).
Cerium oxide nanoparticles (CNPs) have been recently studied for their potent superoxide scavengi... more Cerium oxide nanoparticles (CNPs) have been recently studied for their potent superoxide scavenging properties in both cell and animal model systems. Data from these model systems have shown that exposure of cells to CNPs results in the protection against reactive oxygen species (ROS). Despite these exciting findings, very little is known regarding the uptake or subcellular distribution of these nanomaterials inside cells. In this study we utilized fluorophore (carboxyfluorescein) conjugated cerium oxide NPs (CCNPs) to study the mechanism of uptake and to elucidate the subcellular localization of CNPs using a keratinocyte model system. We observed rapid uptake (within 3 h) of CCNPs that was governed by energy-dependent, clathrinmediated and caveolae-mediated endocytic pathways. We found CCNPs co-localized with mitochondria, lysosomes and endoplasmic reticulum as well as being abundant in the cytoplasm and the nucleus. Given the radical scavenging properties of cerium oxide and the widespread cellular disposition we observed, CNPs likely act as cellular antioxidants in multiple compartments of the cell imparting protection against a variety of oxidant injuries. † Electronic supplementary information (ESI) available: Detailed experimental procedures and supplementary figures are available for this work. See
Nanoparticle technology is undergoing significant expansion largely because of the potential of n... more Nanoparticle technology is undergoing significant expansion largely because of the potential of nanoparticles as biomaterials, drug delivery vehicles, cancer therapeutics, and immunopotentiators. Incorporation of nanoparticle technologies for in vivo applications increases the urgency to characterize nanomaterial immunogenicity. This study explores titanium dioxide, one of the most widely manufactured nanomaterials, synthesized into its three most common nanoarchitectures: anatase (7-10 nm), rutile (15-20 nm), and nanotube (10-15 nm diameters, 70-150 nm length). The fully human autologous MIMIC immunological construct has been utilized as a predictive, nonanimal alternative to diagnose nanoparticle immunogenicity. Cumulatively, treatment with titanium dioxide nanoparticles in the MIMIC system led to elevated levels of proinflammatory cytokines and increased maturation and expression of costimulatory molecules on dendritic cells. Additionally, these treatments effectively primed activation and proliferation of naïve CD4 + T cells in comparison to dendritic cells treated with micrometer-sized (>1 μm) titanium dioxide, characteristic of an in vivo inflammatory response.
This paper explores some of the fundamental and practical issues related to the behavior of nanop... more This paper explores some of the fundamental and practical issues related to the behavior of nanoparticles in the environment and their potential impacts on human health. In our research we have explored the reactive behaviors of nanoparticles with contaminants in the environment, how nanoparticle change in response to their environment and time, and how nanoparticles interact with biological systems of various types. It has become apparent that researchers often underestimate the difficulties of preparing and delivering well characterized nanoparticles for specific types of testing or applications. Difficulties arise in areas that range from not understanding what imparts the “nano” character of a particle to not knowing the impacts of minor species on the properties of high surface area materials. Some of our adventures and misadventures serve as examples of some of these issues as they relate to providing well defined particles for biological studies.
Long term stability and surface properties of colloidal nanoparticles have significance in many a... more Long term stability and surface properties of colloidal nanoparticles have significance in many applications. Here, surface charge modified hydrated cerium oxide nanoparticles (CNPs, also known as nanoceria) are synthesized and their dynamic ion exchange interactions with the surrounding medium are investigated in detail. Time dependent Zeta (ζ) potential (ZP) variations of CNPs are demonstrated as a useful characteristic for optimizing their surface properties. The surface charge reversal of CNPs observed with respect to time, concentration, temperature and doping is correlated to the surface modification of CNPs in aqueous solution and the ion exchange reaction between the surface protons (H + ) and the neighboring hydroxyls ions (OH − ). Using density functional theory (DFT) calculations, we have demonstrated that the adsorption of H + ions on the CNP surface is kinetically more favorable while the adsorption of OH − ions on CNPs is thermodynamically more favorable. The importance of selecting CNPs with appropriate surface charges and the implications of dynamic surface charge variations are exemplified with applications in microelectronics and biomedical.\
Ceria nanoparticles were observed to form star-shaped structures when aged at room temperature in... more Ceria nanoparticles were observed to form star-shaped structures when aged at room temperature in as-synthesized condition. With the help of high resolution transmission electron microscopy (HRTEM), fast Fourier transform (FFT) analyses, and molecular ...
Nanocrystalline Pt/Au/CeO 2 composite electrodes of varying Pt/Au ratios were prepared on polycry... more Nanocrystalline Pt/Au/CeO 2 composite electrodes of varying Pt/Au ratios were prepared on polycrystalline Pt and Au electrodes by simultaneous electrodeposition from K 2 PtCl 6 , AuCl 3 , and CeO 2 solutions. The ratio of Pt:Au was varied from 0:2 to 2:0. It was observed that the electrodes prepared from a 2:1 Pt:Au solution yielded a slightly higher current for the oxidation of methanol. Scanning electron microscopy showed stark changes in the electrode morphology and surface area as the Au concentration is increased. The morphology of the electrodes varies with the ratio of Pt:Au, ranging from a relatively smooth deposit for Pt, a globular particulate for Pt:Au, and a dendrite-like triangular shape for Au. It was also observed that the 1:2 Pt:Au ratio gave a 2-fold increase in the oxidation current for the oxidation of ethanol, suggesting that the Pt:Au composite electrode proves to be a better catalyst for the electrochemical oxidation of ethanol. The changes in morphology of the film can probably be attributed to the catalytic enhancement in ethanol. However, the increase in the current is larger than what can be explained by surface area effects, suggesting a synergistic effect for the electrochemical oxidation of the alcohol.
Nanomaterials synthesized from nanobuilding blocks promise size-dependent properties, associated ... more Nanomaterials synthesized from nanobuilding blocks promise size-dependent properties, associated with individual nanoparticles, together with collective properties of ordered arrays. However, one cannot position nanoparticles at specific locations; rather innovative ways of coaxing these particles to selfassemble must be devised. Conversely, model nanoparticles can be placed in any desired position, which enables a systematic enumeration of nanostructure from model nanobuilding blocks. This is desirable because a list of chemically feasible hypothetical structures will help guide the design of strategies leading to their synthesis.
We predict that the presence of extended defects can reduce the mechanical strength of a ceria na... more We predict that the presence of extended defects can reduce the mechanical strength of a ceria nanorod by 70%. Conversely, the pristine material can deform near its theoretical strength limit. Specifically, atomistic models of ceria nanorods have been generated with full microstructure, including: growth direction, morphology, surface roughening (steps, edges, corners), point defects, dislocations and grain-boundaries. The models were then used to calculate the mechanical strength as a function of microstructure. Our simulations reveal that the compressive yield strengths of ceria nanorods, ca. 10 nm in diameter and without extended defects, are 46 and 36 GPa for rods oriented along [211] and [110] respectively, which represents almost 10% of the bulk elastic modulus and are associated with yield strains of about 0.09. Tensile yield strengths were calculated to be about 50% lower with associated yield strains of about 0.06. For both nanorods, plastic deformation was found to proceed via slip in the {001} plane with direction <110> - a primary slip system for crystals with the fluorite structure. Dislocation evolution for the nanorod oriented along [110] was nucleated via a cerium vacancy present at the surface. A nanorod oriented along [321] and comprising twin-grain boundaries with {111} interfacial planes was calculated to have a yield strength of about 10 GPa (compression and tension) with the grain boundary providing the vehicle for plastic deformation, which slipped in the plane of the grain boundary, with an associated <110> slip direction. We also predict, using a combination of atomistic simulation and DFT, that rutile-structured ceria is feasible when the crystal is placed under tension. The mechanical properties of nanochains, comprising individual ceria nanoparticles with oriented attachment and generated using simulated self-assembly, were found to be similar to those of the nanorod with grain-boundary. Images of the atom positions during tension and compression are shown, together with animations, revealing the mechanisms underpinning plastic deformation. For the nanochain, our simulations help further our understanding of how a crystallising ice front can be used to `sculpt' ceria nanoparticles into nanorods via oriented attachment.We predict that the presence of extended defects can reduce the mechanical strength of a ceria nanorod by 70%. Conversely, the pristine material can deform near its theoretical strength limit. Specifically, atomistic models of ceria nanorods have been generated with full microstructure, including: growth direction, morphology, surface roughening (steps, edges, corners), point defects, dislocations and grain-boundaries. The models were then used to calculate the mechanical strength as a function of microstructure. Our simulations reveal that the compressive yield strengths of ceria nanorods, ca. 10 nm in diameter and without extended defects, are 46 and 36 GPa for rods oriented along [211] and [110] respectively, which represents almost 10% of the bulk elastic modulus and are associated with yield strains of about 0.09. Tensile yield strengths were calculated to be about 50% lower with associated yield strains of about 0.06. For both nanorods, plastic deformation was found to proceed via slip in the {001} plane with direction <110> - a primary slip system for crystals with the fluorite structure. Dislocation evolution for the nanorod oriented along [110] was nucleated via a cerium vacancy present at the surface. A nanorod oriented along [321] and comprising twin-grain boundaries with {111} interfacial planes was calculated to have a yield strength of about 10 GPa (compression and tension) with the grain boundary providing the vehicle for plastic deformation, which slipped in the plane of the grain boundary, with an associated <110> slip direction. We also predict, using a combination of atomistic simulation and DFT, that rutile-structured ceria is feasible when the crystal is placed under tension. The mechanical properties of nanochains, comprising individual ceria nanoparticles with oriented attachment and generated using simulated self-assembly, were found to be similar to those of the nanorod with grain-boundary. Images of the atom positions during tension and compression are shown, together with animations, revealing the mechanisms underpinning plastic deformation. For the nanochain, our simulations help further our understanding of how a crystallising ice front can be used to `sculpt' ceria nanoparticles into nanorods via oriented attachment. Electronic supplementary information (ESI) available: Mechanical deformation of (a) ceria nanorod and (b) nanochain under compression. Calculated Radial Distribution Function associated with the unstrained and strained (comprising rutile polymorph) CeO2[110] nanorod, compared to the RDF associated with the amorphous CeO2 precursor. See DOI: 10.1039/c0nr00980f
Tumorestroma interaction plays an important role in tumor progression. Myofibroblasts, pivotal fo... more Tumorestroma 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 b1 (TGFb1) 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 tumorestroma interaction, thus being a promising strategy for chemoprevention of tumor invasion.
Cerium oxide nanoparticles, nanoceria, are inorganic antioxidants that have catalytic activities ... more Cerium oxide nanoparticles, nanoceria, are inorganic antioxidants that have catalytic activities which mimic those of the neuroprotective enzymes superoxide dismutase and catalase. We have previously shown that nanoceria preserve retinal morphology and prevent loss of retinal function in a rat light damage model. In this study, the homozygous tubby mutant mouse, which exhibits inherited early progressive cochlear and retinal degeneration, was used as a model to test the ability of nanoceria to slow the progression of retinal degeneration. Tubby mice were injected systemically, intracardially, with 20 µl of 1mM nanoceria in saline, at postnatal day 10 and subsequently at P20 and P30 whereas saline injected and uninjected wild type (or heterozygous tubby) served as injected and uninjected controls, respectively. Assays for retinal function, morphology and signaling pathway gene expression were performed on P34 mice. Our data demonstrate that nanoceria protect the retina by decreasing Reactive Oxygen Species (ROS), upregulating the expression of neuroprotection-associated genes; down-regulating apoptosis signaling pathways and/or up-regulating survival signaling pathways to slow photoreceptor degeneration. These data suggest that nanoceria have significant potential as global agents for therapeutic treatment of inherited retinal degeneration and most types of ocular diseases.
Cerium oxide nanoparticles (CNPs) have been demonstrated to protect biological tissues against ra... more Cerium oxide nanoparticles (CNPs) have been demonstrated to protect biological tissues against radiation induced damage and scavenging of superoxide anions, prevent laser induced retinal damage, reduce spinal injury, possess pH dependent antioxidant properties, prevent cardiovascular myopathy, and as a tool for immunoassays and other inflammatory diseases.1a-j It is speculated that nanoceria is a regenerative radical scavenger with the ability to regenerate the active Ce 3+ oxidation state for radical scavenging which separates it from other nanomaterials based antioxidant systems such as hydroxylated and water-soluble C-60 and SWCNTs.1k, l Thus far there are no reports on controlling the regeneration of the Ce 3+ oxidation state which is the most important parameter in the application of CNPs as a reliable, regenerative radical scavenger. There is an imminent need to increase the residence time of CNPs in the body and to control the regeneration of the Ce 3+ oxidation state. PEG has been reported to increase the residence time of NPs and proteins inside cells and provide biocom-patibility.2 PEGylated counterparts of the Superoxide Dismutase (SOD) enzymes have shown improved performance over non-PEGylated enzymes. 2 Herein, we report our efforts to synthesize CNPs directly in PEG (600 MW) solution and determine the effect of increasing [PEG] (PEG vol % as 5, 10, 20, 40, 60, and 80) on the SOD mimetic properties exhibited by nanoceria. We also report how the active Ce 3+ oxidation state can be regenerated and demonstrate the role of PEG on the redox chemistry of CNPs catalyzed by H 2 O 2 . Several complexes of PEGs with lanthanides have been reported and characterized.3 To evaluate the effect of [PEG] on the complexation of cerium, UV-vis spectra of the precursor salt of cerium (cerium nitrate hexahydrate) in different solutions of PEG were obtained (SI-1). All PEG solutions show higher absorption relative to the water based solution of cerium nitrate, but the observed nonspecific trend could not be ascribed to a systematic decrease in the solvent polarity or dielectric constant. This observation indicates the complexation of cerium ions with PEG. In contrast to this Uekawa et al.4a, b reported a red shift upon addition of cerium nitrate in PEG and ascribed the red shift to the complexation of PEG with cerium ions. The CNPs were synthesized as described in the experimental details (SI-2). A high resolution transmission electron micrograph
The formation of nanorods, driven by the physicochemical phenomena during the freezing and after ... more The formation of nanorods, driven by the physicochemical phenomena during the freezing and after the aging of frozen ceria nanoparticle suspensions, is reported. During freezing of a dilute aqueous solution of CeO2 nanocrystals, some nuclei remain in solution while others are trapped inside micro- and nanometer voids formed within the growing ice front. Over time (2-3 weeks) the particles trapped within the nanometer-wide voids in the ice combine by an oriented attachment process to form ceria nanorods. The experimental observations are consistent with molecular dynamics simulations of particle aggregation in constrained environments. These observations suggest a possible strategy for the templated formation of nanostructures through self-assembly by exploiting natural phenomena, such as voids formed during freezing of water. This research suggests a very simple, green chemical route to guide the formation of one- and three-dimensional self-assembled nanostructures.
In this study we have found that cerium oxide nanoparticles exhibit catalase mimetic activity. Su... more In this study we have found that cerium oxide nanoparticles exhibit catalase mimetic activity. Surprisingly, the catalase mimetic activity correlates with a reduced level of cerium in the +3 state, in contrast to the relationship between surface charge and superoxide scavenging properties.
A solution precursor plasma spray (SPPS) technique has been used for direct deposition of cerium ... more A solution precursor plasma spray (SPPS) technique has been used for direct deposition of cerium oxide nanoparticles (CNPs) from various cerium salt solutions as precursors. Solution precursors were injected into the hot zone of a plasma plume to deposit CNP coatings. A numerical study of the droplet injection model has been employed for microstructure development during SPPS. The decomposition of each precursor to cerium oxide was analyzed by thermogravimetric-differential thermal analysis and validated by thermodynamic calculations. The presence of the cerium oxide phase in the coatings was confirmed by X-ray diffraction studies. Transmission electron microscopy studies confirmed nanocrystalline (grain size <14 nm) characteristic of the coatings. X-ray photoelectron spectroscopy studies indicated the presence of a high concentration of Ce3+ (up to 0.32) in the coating prepared by SPPS. The processing and microstructure evolution of cerium oxide coatings with high nonstoichiometry are reported.
A room temperature, template-free, wet chemical synthesis of ceria nanoparticles and their long t... more 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.
Reactive oxygen and nitrogen species play a critical role in many degenerative diseases and in ag... more Reactive oxygen and nitrogen species play a critical role in many degenerative diseases and in aging. Nanomaterials, especially modified fullerenes and cerium oxide nanoparticles, have been shown to effectively protect mammalian cells against damage caused by increased reactive oxygen or nitrogen species, likely through their direct reaction with superoxide radical, since each of these materials has been shown to act as effective superoxide dismutase mimetics in vitro. This critical review discusses the chemistry of these nanomaterials and the context in which their radical scavenging activities have been studied in biological model systems. Current studies are focused on determining the uptake, metabolism, distribution, toxicity and fate of these nanomaterials in cell and animal model systems. Ultimately if shown to be safe, these nanomaterials have the potential to be used to reduce the damaging effects of radicals in biological systems (101 references).
Cerium oxide nanoparticles (CNPs) have been recently studied for their potent superoxide scavengi... more Cerium oxide nanoparticles (CNPs) have been recently studied for their potent superoxide scavenging properties in both cell and animal model systems. Data from these model systems have shown that exposure of cells to CNPs results in the protection against reactive oxygen species (ROS). Despite these exciting findings, very little is known regarding the uptake or subcellular distribution of these nanomaterials inside cells. In this study we utilized fluorophore (carboxyfluorescein) conjugated cerium oxide NPs (CCNPs) to study the mechanism of uptake and to elucidate the subcellular localization of CNPs using a keratinocyte model system. We observed rapid uptake (within 3 h) of CCNPs that was governed by energy-dependent, clathrinmediated and caveolae-mediated endocytic pathways. We found CCNPs co-localized with mitochondria, lysosomes and endoplasmic reticulum as well as being abundant in the cytoplasm and the nucleus. Given the radical scavenging properties of cerium oxide and the widespread cellular disposition we observed, CNPs likely act as cellular antioxidants in multiple compartments of the cell imparting protection against a variety of oxidant injuries. † Electronic supplementary information (ESI) available: Detailed experimental procedures and supplementary figures are available for this work. See
Nanoparticle technology is undergoing significant expansion largely because of the potential of n... more Nanoparticle technology is undergoing significant expansion largely because of the potential of nanoparticles as biomaterials, drug delivery vehicles, cancer therapeutics, and immunopotentiators. Incorporation of nanoparticle technologies for in vivo applications increases the urgency to characterize nanomaterial immunogenicity. This study explores titanium dioxide, one of the most widely manufactured nanomaterials, synthesized into its three most common nanoarchitectures: anatase (7-10 nm), rutile (15-20 nm), and nanotube (10-15 nm diameters, 70-150 nm length). The fully human autologous MIMIC immunological construct has been utilized as a predictive, nonanimal alternative to diagnose nanoparticle immunogenicity. Cumulatively, treatment with titanium dioxide nanoparticles in the MIMIC system led to elevated levels of proinflammatory cytokines and increased maturation and expression of costimulatory molecules on dendritic cells. Additionally, these treatments effectively primed activation and proliferation of naïve CD4 + T cells in comparison to dendritic cells treated with micrometer-sized (>1 μm) titanium dioxide, characteristic of an in vivo inflammatory response.
This paper explores some of the fundamental and practical issues related to the behavior of nanop... more This paper explores some of the fundamental and practical issues related to the behavior of nanoparticles in the environment and their potential impacts on human health. In our research we have explored the reactive behaviors of nanoparticles with contaminants in the environment, how nanoparticle change in response to their environment and time, and how nanoparticles interact with biological systems of various types. It has become apparent that researchers often underestimate the difficulties of preparing and delivering well characterized nanoparticles for specific types of testing or applications. Difficulties arise in areas that range from not understanding what imparts the “nano” character of a particle to not knowing the impacts of minor species on the properties of high surface area materials. Some of our adventures and misadventures serve as examples of some of these issues as they relate to providing well defined particles for biological studies.
Long term stability and surface properties of colloidal nanoparticles have significance in many a... more Long term stability and surface properties of colloidal nanoparticles have significance in many applications. Here, surface charge modified hydrated cerium oxide nanoparticles (CNPs, also known as nanoceria) are synthesized and their dynamic ion exchange interactions with the surrounding medium are investigated in detail. Time dependent Zeta (ζ) potential (ZP) variations of CNPs are demonstrated as a useful characteristic for optimizing their surface properties. The surface charge reversal of CNPs observed with respect to time, concentration, temperature and doping is correlated to the surface modification of CNPs in aqueous solution and the ion exchange reaction between the surface protons (H + ) and the neighboring hydroxyls ions (OH − ). Using density functional theory (DFT) calculations, we have demonstrated that the adsorption of H + ions on the CNP surface is kinetically more favorable while the adsorption of OH − ions on CNPs is thermodynamically more favorable. The importance of selecting CNPs with appropriate surface charges and the implications of dynamic surface charge variations are exemplified with applications in microelectronics and biomedical.\
Ceria nanoparticles were observed to form star-shaped structures when aged at room temperature in... more Ceria nanoparticles were observed to form star-shaped structures when aged at room temperature in as-synthesized condition. With the help of high resolution transmission electron microscopy (HRTEM), fast Fourier transform (FFT) analyses, and molecular ...
Nanocrystalline Pt/Au/CeO 2 composite electrodes of varying Pt/Au ratios were prepared on polycry... more Nanocrystalline Pt/Au/CeO 2 composite electrodes of varying Pt/Au ratios were prepared on polycrystalline Pt and Au electrodes by simultaneous electrodeposition from K 2 PtCl 6 , AuCl 3 , and CeO 2 solutions. The ratio of Pt:Au was varied from 0:2 to 2:0. It was observed that the electrodes prepared from a 2:1 Pt:Au solution yielded a slightly higher current for the oxidation of methanol. Scanning electron microscopy showed stark changes in the electrode morphology and surface area as the Au concentration is increased. The morphology of the electrodes varies with the ratio of Pt:Au, ranging from a relatively smooth deposit for Pt, a globular particulate for Pt:Au, and a dendrite-like triangular shape for Au. It was also observed that the 1:2 Pt:Au ratio gave a 2-fold increase in the oxidation current for the oxidation of ethanol, suggesting that the Pt:Au composite electrode proves to be a better catalyst for the electrochemical oxidation of ethanol. The changes in morphology of the film can probably be attributed to the catalytic enhancement in ethanol. However, the increase in the current is larger than what can be explained by surface area effects, suggesting a synergistic effect for the electrochemical oxidation of the alcohol.
Nanomaterials synthesized from nanobuilding blocks promise size-dependent properties, associated ... more Nanomaterials synthesized from nanobuilding blocks promise size-dependent properties, associated with individual nanoparticles, together with collective properties of ordered arrays. However, one cannot position nanoparticles at specific locations; rather innovative ways of coaxing these particles to selfassemble must be devised. Conversely, model nanoparticles can be placed in any desired position, which enables a systematic enumeration of nanostructure from model nanobuilding blocks. This is desirable because a list of chemically feasible hypothetical structures will help guide the design of strategies leading to their synthesis.
We predict that the presence of extended defects can reduce the mechanical strength of a ceria na... more We predict that the presence of extended defects can reduce the mechanical strength of a ceria nanorod by 70%. Conversely, the pristine material can deform near its theoretical strength limit. Specifically, atomistic models of ceria nanorods have been generated with full microstructure, including: growth direction, morphology, surface roughening (steps, edges, corners), point defects, dislocations and grain-boundaries. The models were then used to calculate the mechanical strength as a function of microstructure. Our simulations reveal that the compressive yield strengths of ceria nanorods, ca. 10 nm in diameter and without extended defects, are 46 and 36 GPa for rods oriented along [211] and [110] respectively, which represents almost 10% of the bulk elastic modulus and are associated with yield strains of about 0.09. Tensile yield strengths were calculated to be about 50% lower with associated yield strains of about 0.06. For both nanorods, plastic deformation was found to proceed via slip in the {001} plane with direction <110> - a primary slip system for crystals with the fluorite structure. Dislocation evolution for the nanorod oriented along [110] was nucleated via a cerium vacancy present at the surface. A nanorod oriented along [321] and comprising twin-grain boundaries with {111} interfacial planes was calculated to have a yield strength of about 10 GPa (compression and tension) with the grain boundary providing the vehicle for plastic deformation, which slipped in the plane of the grain boundary, with an associated <110> slip direction. We also predict, using a combination of atomistic simulation and DFT, that rutile-structured ceria is feasible when the crystal is placed under tension. The mechanical properties of nanochains, comprising individual ceria nanoparticles with oriented attachment and generated using simulated self-assembly, were found to be similar to those of the nanorod with grain-boundary. Images of the atom positions during tension and compression are shown, together with animations, revealing the mechanisms underpinning plastic deformation. For the nanochain, our simulations help further our understanding of how a crystallising ice front can be used to `sculpt' ceria nanoparticles into nanorods via oriented attachment.We predict that the presence of extended defects can reduce the mechanical strength of a ceria nanorod by 70%. Conversely, the pristine material can deform near its theoretical strength limit. Specifically, atomistic models of ceria nanorods have been generated with full microstructure, including: growth direction, morphology, surface roughening (steps, edges, corners), point defects, dislocations and grain-boundaries. The models were then used to calculate the mechanical strength as a function of microstructure. Our simulations reveal that the compressive yield strengths of ceria nanorods, ca. 10 nm in diameter and without extended defects, are 46 and 36 GPa for rods oriented along [211] and [110] respectively, which represents almost 10% of the bulk elastic modulus and are associated with yield strains of about 0.09. Tensile yield strengths were calculated to be about 50% lower with associated yield strains of about 0.06. For both nanorods, plastic deformation was found to proceed via slip in the {001} plane with direction <110> - a primary slip system for crystals with the fluorite structure. Dislocation evolution for the nanorod oriented along [110] was nucleated via a cerium vacancy present at the surface. A nanorod oriented along [321] and comprising twin-grain boundaries with {111} interfacial planes was calculated to have a yield strength of about 10 GPa (compression and tension) with the grain boundary providing the vehicle for plastic deformation, which slipped in the plane of the grain boundary, with an associated <110> slip direction. We also predict, using a combination of atomistic simulation and DFT, that rutile-structured ceria is feasible when the crystal is placed under tension. The mechanical properties of nanochains, comprising individual ceria nanoparticles with oriented attachment and generated using simulated self-assembly, were found to be similar to those of the nanorod with grain-boundary. Images of the atom positions during tension and compression are shown, together with animations, revealing the mechanisms underpinning plastic deformation. For the nanochain, our simulations help further our understanding of how a crystallising ice front can be used to `sculpt' ceria nanoparticles into nanorods via oriented attachment. Electronic supplementary information (ESI) available: Mechanical deformation of (a) ceria nanorod and (b) nanochain under compression. Calculated Radial Distribution Function associated with the unstrained and strained (comprising rutile polymorph) CeO2[110] nanorod, compared to the RDF associated with the amorphous CeO2 precursor. See DOI: 10.1039/c0nr00980f
Tumorestroma interaction plays an important role in tumor progression. Myofibroblasts, pivotal fo... more Tumorestroma 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 b1 (TGFb1) 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 tumorestroma interaction, thus being a promising strategy for chemoprevention of tumor invasion.
Cerium oxide nanoparticles, nanoceria, are inorganic antioxidants that have catalytic activities ... more Cerium oxide nanoparticles, nanoceria, are inorganic antioxidants that have catalytic activities which mimic those of the neuroprotective enzymes superoxide dismutase and catalase. We have previously shown that nanoceria preserve retinal morphology and prevent loss of retinal function in a rat light damage model. In this study, the homozygous tubby mutant mouse, which exhibits inherited early progressive cochlear and retinal degeneration, was used as a model to test the ability of nanoceria to slow the progression of retinal degeneration. Tubby mice were injected systemically, intracardially, with 20 µl of 1mM nanoceria in saline, at postnatal day 10 and subsequently at P20 and P30 whereas saline injected and uninjected wild type (or heterozygous tubby) served as injected and uninjected controls, respectively. Assays for retinal function, morphology and signaling pathway gene expression were performed on P34 mice. Our data demonstrate that nanoceria protect the retina by decreasing Reactive Oxygen Species (ROS), upregulating the expression of neuroprotection-associated genes; down-regulating apoptosis signaling pathways and/or up-regulating survival signaling pathways to slow photoreceptor degeneration. These data suggest that nanoceria have significant potential as global agents for therapeutic treatment of inherited retinal degeneration and most types of ocular diseases.
Cerium oxide nanoparticles (CNPs) have been demonstrated to protect biological tissues against ra... more Cerium oxide nanoparticles (CNPs) have been demonstrated to protect biological tissues against radiation induced damage and scavenging of superoxide anions, prevent laser induced retinal damage, reduce spinal injury, possess pH dependent antioxidant properties, prevent cardiovascular myopathy, and as a tool for immunoassays and other inflammatory diseases.1a-j It is speculated that nanoceria is a regenerative radical scavenger with the ability to regenerate the active Ce 3+ oxidation state for radical scavenging which separates it from other nanomaterials based antioxidant systems such as hydroxylated and water-soluble C-60 and SWCNTs.1k, l Thus far there are no reports on controlling the regeneration of the Ce 3+ oxidation state which is the most important parameter in the application of CNPs as a reliable, regenerative radical scavenger. There is an imminent need to increase the residence time of CNPs in the body and to control the regeneration of the Ce 3+ oxidation state. PEG has been reported to increase the residence time of NPs and proteins inside cells and provide biocom-patibility.2 PEGylated counterparts of the Superoxide Dismutase (SOD) enzymes have shown improved performance over non-PEGylated enzymes. 2 Herein, we report our efforts to synthesize CNPs directly in PEG (600 MW) solution and determine the effect of increasing [PEG] (PEG vol % as 5, 10, 20, 40, 60, and 80) on the SOD mimetic properties exhibited by nanoceria. We also report how the active Ce 3+ oxidation state can be regenerated and demonstrate the role of PEG on the redox chemistry of CNPs catalyzed by H 2 O 2 . Several complexes of PEGs with lanthanides have been reported and characterized.3 To evaluate the effect of [PEG] on the complexation of cerium, UV-vis spectra of the precursor salt of cerium (cerium nitrate hexahydrate) in different solutions of PEG were obtained (SI-1). All PEG solutions show higher absorption relative to the water based solution of cerium nitrate, but the observed nonspecific trend could not be ascribed to a systematic decrease in the solvent polarity or dielectric constant. This observation indicates the complexation of cerium ions with PEG. In contrast to this Uekawa et al.4a, b reported a red shift upon addition of cerium nitrate in PEG and ascribed the red shift to the complexation of PEG with cerium ions. The CNPs were synthesized as described in the experimental details (SI-2). A high resolution transmission electron micrograph
The formation of nanorods, driven by the physicochemical phenomena during the freezing and after ... more The formation of nanorods, driven by the physicochemical phenomena during the freezing and after the aging of frozen ceria nanoparticle suspensions, is reported. During freezing of a dilute aqueous solution of CeO2 nanocrystals, some nuclei remain in solution while others are trapped inside micro- and nanometer voids formed within the growing ice front. Over time (2-3 weeks) the particles trapped within the nanometer-wide voids in the ice combine by an oriented attachment process to form ceria nanorods. The experimental observations are consistent with molecular dynamics simulations of particle aggregation in constrained environments. These observations suggest a possible strategy for the templated formation of nanostructures through self-assembly by exploiting natural phenomena, such as voids formed during freezing of water. This research suggests a very simple, green chemical route to guide the formation of one- and three-dimensional self-assembled nanostructures.
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Papers by Ajay Karakoti