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The stability of microRNA-146a conjugated with different nanoparticles in the presence of high oxidative stress was investigated through detailed electroanalysis.

There is intense interest in developing long-lasting, potent, and broad-spectrum antiviral disinfectants. Ceria nanoparticles (CNPs) can undergo surface redox reactions (Ce3+ ↔ Ce4+) to generate ROS without requiring an external driving force. Here, we tested the mechanism behind our prior finding of potent inactivation of enveloped and non-enveloped RNA viruses by silver-modified CNPs, AgCNP1 and AgCNP2. Treatment of human respiratory viruses, coronavirus OC43 and parainfluenza virus type 5 (PIV5) with AgCNP1 and 2, respectively, prevented virus interactions with host cell receptors and resulted in virion aggregation. Rhinovirus 14 (RV14) mutants were selected to be resistant to inactivation by AgCNP2. Sequence analysis of the resistant virus genomes predicted two amino acid changes in surface-located residues D91V and F177L within capsid protein VP1. Consistent with the regenerative properties of CNPs, surface-applied AgCNP1 and 2 inactivated a wide range of structurally diverse viruses, including enveloped (OC43, SARS-CoV-2, and PIV5) and non-enveloped RNA viruses (RV14 and feline calicivirus; FCV). Remarkably, a single application of AgCNP1 and 2 potently inactivated up to four sequential rounds of virus challenge. Our results show broad-spectrum and long-lasting anti-viral activity of AgCNP nanoparticles, due to targeting of viral surface proteins to disrupt interactions with cellular receptors.

The number of diabetics is increasing worldwide and is associated with significant instances of clinical morbidity. Increased amounts of reactive oxygen species (ROS) and proinflammatory cytokines are associated with the pathogenesis of diabetic wounds and result in a significant delay in healing. Our previous studies have shown the ability of a cerium oxide nanoparticle (CNP) formulation conjugated with the anti-inflammatory microRNA miR146a (CNP-miR146a) to enhance the healing of diabetic wounds. The observed therapeutic activity exceeded the combined efficacies of the individual conjugate components (CNPs and miR146a alone), suggesting a synergistic effect. The current study evaluates whether the previously observed enhanced activity arises from increased agent delivery (simple nanocarrier activity) or is specific to the CNP-miR146a formulation (functional, bio-active nanomaterial). Comparison with miR146a conjugated gold (bioactive, metal) and silica (bioinert, oxide) nanoparticles (AuNPs and SiO

While research into Drug-Target Interaction (DTI) prediction is fairly mature, generalizability and interpretability are not always addressed in the existing works in this field. In this paper, we propose a deep learning-based framework, called BindingSite-AugmentedDTA, which improves Drug-Target Affinity (DTA) predictions by reducing the search space of potential binding sites of the protein, thus making the binding affinity prediction more efficient and accurate. Our BindingSite-AugmentedDTA is highly generalizable as it can be integrated with any DL-based regression model, while it significantly improves their prediction performance. Also, unlike many existing models, our model is highly interpretable due to its architecture and self-attention mechanism, which can provide a deeper understanding of its underlying prediction mechanism by mapping attention weights back to protein binding sites. The computational results confirm that our framework can enhance the prediction performance of seven state-of-the-art DTA prediction algorithms in terms of 4 widely used evaluation metrics, including Concordance Index (CI), Mean Squared Error (MSE), modified squared correlation coefficient , and the Area Under the Precision Curve (AUPC). We also contribute to the two most commonly used DTA benchmark datasets, namely Kiba and Davis, by including additional information on 3D structure of all proteins contained in these two datasets. We manually extracted this information from Protein Data Bank (PDB) files of proteins available at https://www.uniprot.org/. Furthermore, we experimentally validate the practical potential of our proposed framework through in-lab experiments. We measure the binding interaction between several drug candidate compounds for the inhibition of binding between (SARS-CoV-2 S-protein RBD) Spike and ACE-2 (host cell binding target) proteins. We then compare the computationally-predicted results against the ones experimentally-observed in the laboratory. The relatively high agreement between computationally-predicted and experimentally-observed binding interactions supports the potential of our framework as the next-generation pipeline for prediction models in drug repurposing.

The COVID-19 pandemic marks an inflection point in the perception and treatment of human health. Substantial resources have been reallocated to address the direct medical effects of COVID-19 and to curtail the spread of the virus. Thereby, shortcomings of traditional disinfectants, especially their requirement for regular reapplication and the related complications (e.g., dedicated personnel and short-term activity), have become issues at the forefront of public health concerns. This issue became especially pressing when infection-mitigating supplies dwindled early in the progression of the pandemic. In consideration of the constant threat posed by emerging novel viruses, we report a platform technology for persistent surface disinfection to combat virus transmission through nanomaterial-mediated, localized UV radiation emission. In this work, two formulations of Y

In this study, we introduce and implement an interpretable graph-based deep learning prediction model, which utilizes protein binding sites along with self-attention to learn which protein binding sites interact with a given ligand. Our proposed model enables interpretability by identifying the protein binding sites that contribute the most towards the Drug-Target Interaction. Results on three benchmark datasets show improved performance compared to previous graph-based models. More significantly, unlike previous studies our model performance remains close to the optimal performance when tested with new proteins (ie., high generalizablity). Through multidisciplinary collaboration, we further experimentally evaluate the practical potential of our proposed approach. To achieve this, we first computationally predict binding interaction of some candidate compounds with a target protein, then experimentally validate the binding interactions for these pairs in the laboratory. The high agreement between the computationally-predicted and experimentally-observed (measured) DTIs illustrates the potential of our method as an effective pre-screening tool in drug re-purposing applications.

The COVID19 pandemic has brought global attention to the threat of emerging viruses and to antiviral therapies, in general. In particular, the high transmissibility and infectivity of respiratory viruses have been brought to the general public's attention, along with the need for highly effective antiviral and disinfectant materials/products. This study has developed two distinct silver-modified formulations of redox-active nanoscale cerium oxide (AgCNP1 and AgCNP2). The formulations show specific antiviral activities toward tested OC43 coronavirus and RV14 rhinovirus pathogens, with materials characterization demonstrating a chemically stable character for silver nanophases on ceria particles and significant differences in Ce3+/Ce4+ redox state ratio (25.8 and 53.7% Ce3+ for AgCNP1 & 2, respectively). In situ electrochemical studies further highlight differences in formulation-specific viral inactivation and suggest specific modes of action. Altogether, the results from this study support the utility of AgCNP formulations as high stability, high efficacy materials for use against clinically relevant virus species.

Designing hybrid conductive polymer structures that can effectively mitigate capacitance fade and improve cycle life is critical to developing viable conductive polymer-based supercapacitors. Low cost and high yield synthesis methods that can be easily scaled-up are also crucial for industry-scale production. Herein, we report a highly scalable porous hierarchical microspheres composed of polyaniline nanofibers (PANI), reduced graphene oxide (rGO), and cerium oxide nanorods (CNRs) synthesized through a spray drying method. The functional and structural synergistic effect of the three components assembled as a 3D porous hierarchical structure which maximizes ion and charge transport while mitigating restacking and agglomeration of the nanostructures results in a composite supercapacitor material with superior electrochemical properties. The optimized ternary hierarchical microspheres exhibit a high specific capacitance (684 F g−1), good rate capability, excellent cycle life (92% capacitance retention after 6000 cycles at 4 A g−1). Furthermore, an asymmetric device fabricated with the ternary composite exhibits a high specific energy density (46.27 W h kg−1) at a power density of 850 W kg−1 with a very stable cyclic performance and high coulombic efficiency. Thus, we demonstrate, for the first time, a highly scalable method to produce PANI/rGO/CNR based hierarchical microspheres as high-performance supercapacitor material.

Herein, we provide the first account of a method to control cerium oxide's mixed valence states (as Ce3+ to Ce4+ ratio) in ultra-thin films formed via atomic layer deposition (ALD). It is determined that modulation of Ce3+/Ce4+ ratio occurs with respect to film thickness and is analogous to the change in surface chemistry observed for cerium oxide nanoparticles with varying particle diameter. The influence of film thickness on enzyme-mimetic radical scavenging is also characterized. Higher film thicknesses show 9-fold increase in catalytic activity. In vitro biocompatibility (apoptosis < 4%) and electrochemical biosensing (lowest concentration: 18 ppt) studies were performed to demonstrate the potential of ALD-grown nanoceria films for biomedical applications.

Oxidative stress increases bone loss and limits repair, in part, through immunoregulation and the formation and maintenance of low-grade chronic inflammation. The aim of this study was to investigate the effect of cerium oxide nanoparticles (CeONPs) on (i) macrophage phenotype and cytokine expression under normal and simulated acute and chronic inflammatory conditions and, (ii) human mesenchymal stem cell (hBMSCs) proliferation, osteoinduction and osteogenic differentiation. Spherical particles composed of 60% Ce3+ with a hydrodynamic size of ~35 nm and surface charge of 25.4 mV were internalized within cells. Under both acute and chronic conditions, inducible nitric oxide synthase (iNOS) activity decreased with a significant reduction seen in the 1 and 10 μg/mL groups (p

Nanocrystalline cerium oxide (nanoceria) is a rare earth oxide with a complex surface chemistry. This material has seen substantial investigation in recent years in both fundamental and applied studies due largely to more precise characterization of the unique surface structures, which mediate its pronounced redox activity. In particular, oxygen storage/buffering capacities have been thoroughly correlated with synthesis and processing condition effects on other material features such as surface (micro-) faceting, reconstruction, and (extent of) hydration. Key material features such as these modulate nanoceria redox performance by changing the crystal microenvironment. In this review, we present nanoengineering methods, which have produced increased nanoceria performance in biomedical, energy, and catalysis applications. The impact of combined/cooperative theoretical and experimental studies are highlighted throughout.

Laboratory and experimental scale manufacturing processes are limited by human error (e.g., poor control over motion and personal subjectivity), especially under fatiguing conditions involving precise, repetitive operations, incurring compounding errors. Commercial layer-by-layer (LbL) automation devices are prohibitively high-priced (especially for academic institutions) with limited flexibility in form factor and potentially software-associated constraints/limitations. In this work, a novel automated multi-beaker dip coater was fabricated to facilitate nano cerium oxide/polymer coatings via an LbL dip coating process and the synthesis of nano ceria films via a novel successive ionic layer adsorption and reaction method on a glass substrate. Automation of tasks, such as those mediating the detailed procedures, is essential in producing highly reproducible, consistent products/materials as well as in reducing the time commitments for laboratory researchers. Herein, we detail the construction of a relatively large, yet inexpensive, LbL coating instrument that can operate over 90 cm in the horizontal axis, allowing, for example, up to eight 200 ml beakers with accompanying stir plates. The instrument is operated by simple "off-the-shelf" electronics to control the path and timing of the samples with open-source software while providing precision at ±0.01 mm. Furthermore, 3D-printed components were used to maximize the number of substrates that could be coated simultaneously, further improving the sample production rate and reducing waste. Further possibilities for automation beyond the detailed device are provided and discussed, including software interfaces, physical control methods, and sensors for data collection/analysis or for triggers of automated tasks.

Increased bone loss and risk of fracture are two of the main challenges for cancer patients who undergo ionizing radiation (IR) therapy. This decline in bone quality is in part, caused by the excessive and sustained release of reactive oxygen species (ROS). Cerium oxide nanoparticles (CeONPs) have proven antioxidant and regenerative properties and the purpose of this study was to investigate the effect of CeONPs in reducing IR-induced functional damage in human bone marrow-derived mesenchymal stromal cells (hBMSCs). hBMSCs were supplemented with CeONPs at a concentration of either 1 or 10 μg/mL 24 h prior to exposure to a single 7 Gy irradiation dose. ROS levels, cellular proliferation, morphology, senescence, DNA damage, p53 expression and autophagy were evaluated as well as alkaline phosphatase, osteogenic protein gene expression and bone matrix deposition following osteogenic differentiation. Results showed that supplementation of CeONPs at a concentration of 1 μg/mL reduced cell senescence and significantly augmented cell autophagy (p = 0.01), osteogenesis and bone matrix deposition2-fold (p = 0.0001) while under normal, non-irradiated culture conditions. Following irradiation, functional damage was attenuated and CeONPs at both 1 or 10 μg/mL significantly reduced ROS levels (p = 0.05 and 0.001 respectively), DNA damage by4-fold (p 0.05) while increasing autophagy3.5-fold and bone matrix deposition 5-fold (p = 0.0001 in both groups). When supplemented with 10 μg/mL, p53 expression increased 3.5-fold (p 0.05). We conclude that cellular uptake of CeONPs offered a significant, multifunctional and protective effect against IR-induced cellular damage while also augmenting osteogenic differentiation and subsequent new bone deposition. The use of CeONPs holds promise as a novel multifunctional therapeutic strategy for irradiation-induced bone loss.

In this study, several formulations of nanoceria and dextran-nanoceria with curcumin, each demonstrated to have anti-cancer properties, were synthesized and applied as treatment for human childhood neuroblastoma. The anti-cancer activities of these formulations were explored in neuroblastoma models of both MYCN-amplified and non-amplified cell lines. Ceria nanoparticles, coated with dextran and loaded with curcumin, were found to induce substantial cell death in neuroblastoma cells (up to a 2-fold and a 1.6-fold decrease in cell viability for MYCN-upregulated and normal expressing cell lines, respectively; *p < 0.05) while producing no or only minor toxicity in healthy cells (no toxicity at 100 μM; **p < 0.01). This formulation evokes prolonged oxidative stress, stabilizing HIF-1α, and inducing caspase-dependent apoptosis (up to a 2.4-fold increase over control; *p < 0.05). Overall, nano-therapeutic treatments showed a more pronounced effect in MYCN-amplified cells, which are traditionally more resistant to drug therapies. These results represent a very promising alternative to small molecule drug therapies for robust cancers.

The Ultraviolet-B radiation (UVB) might induce cellular redox imbalance which plays an important role in the development of skin disorders. Thus, the search for photochemoprotective alternatives with antioxidant efficacy would be a safe aspect towards prevention of skin diseases. Cerium oxide nanoparticles (CNPs) have antioxidant properties, that are mostly related to CNPs catalase and superoxide dismutase (SOD)-like antioxidative mimetic activity. Considering that, we investigated whether CNPs induce photochemoprotection against UVB-induced cellular damages on L929 fibroblasts. Our results showed that CNPs prevented UVB mediated L929 cell oxidative damage by reestablishing the oxidative balance through ameliorating the reactive oxygen species (ROS) level and enhancing the antioxidant enzyme activities.

The catalytic activity of cerium oxide nanoparticles (CNPs) depends on the surface Ce3+/Ce4+ oxidation state. CNPs with a higher Ce3+ to Ce4+ ratio, oxygen vacancies and higher superoxide dismutase (SOD) mimetic activity are more effective against diseases associated with oxidative stress or inflammation. CNPs with a lower Ce3+/Ce4+ ratio show higher catalase mimetic activity and possess anticancer/antibacterial activity. However, different synthesis methods of CNPs and capping agents/surface coatings result in various Ce3+/Ce4+ oxidation states, thus limiting the use of particular CNPs for specific biological applications. In this study, we have shown that by selecting an appropriate doping method we can control the surface Ce3+/Ce4+ oxidation state to tune the catalytic activity and biological response. Importantly, superior SOD mimetic activity and efficient reactive oxygen species scavenging capability of one-step synthesized CNPs are linked to a uniform distribution of dopants in the CNP lattice and changes in the surface Ce3+/Ce4+ oxidation state.

Effectively controlling vector mosquito populations while avoiding the development of resistance remains a prevalent and increasing obstacle to integrated vector management. Although, metallic nanoparticles have previously shown promise in controlling larval populations via mechanisms which are less likely to spur resistance, the impacts of such particles on life history traits and fecundity of mosquitoes are understudied. Herein, we investigate the chemically well-defined cerium oxide nanoparticles (CNPs) and silver-doped nanoceria (AgCNPs) for larvicidal potential and effects on life history traits and fecundity of Aedes (Ae.) aegypti mosquitoes. When 3rd instar larvae were exposed to nanoceria in absence of larval food, the mortality count disclosed significant activity of AgCNPs over CNPs (57.8±3.68% and 17.2±2.81% lethality, respectively) and a comparable activity to Ag+ controls (62.8±3.60% lethality). The surviving larvae showed altered life history traits (e.g., reduced egg hatch proportion and varied sex ratios), indicating activities of these nanoceria beyond just that of a larvicide. In a separate set of experiments, impacts on oocyte growth and egg generation resulting from nanoceria-laced blood meals were studied using confocal fluorescence microscopy revealing oocytes growth-arrest at 16-24h after feeding with AgCNP-blood meals in some mosquitoes, thereby significantly reducing average egg clutch. AgCNPs caused ~60% mortality in 3rd instar larvae when larval food was absent, while CNPs yielded only ~20% mortality which contrasts with a previous report on green-synthesized nanoceria and highlights the level of detail required to accurately report and interpret such studies. Additionally, AgCNPs are estimated to contain much less silver (0.22 parts per billion, ppb) than the amount of Ag+ needed to achieve comparable larvicidal activity (2.7 parts per million, ppm), potentially making these nanoceria ecofriendly. Finally, this work is the first study to demonstrate the until-now-unappreciated impacts of nanoceria on life history traits and interference with mosquito egg development., Author summary Viral diseases like Zika and dengue fevers that are vectored by mosquitoes cause illness and death in populations worldwide. Chemical pesticides are the frontline tools used to control mosquitoes, however, development of resistance by the vectors to these agents overtime ultimately reduces effectiveness. Hence, the development of new pesticides that do not spur the development of resistance is of paramount importance. We therefore developed and characterized various types of well-defined cerium oxide nanoparticles (nanoceria) and studied the impacts on Aedes (Ae.) aegypti mosquitoes resulting from exposure to these novel agents. We found that nanoceria not only have larvicidal potential, but also alter the life history traits (e.g., reduced egg hatch proportion and altered sex ratio) of the subsequent adult mosquitoes exposed to these nanoparticles during the larval stage. One of the most interesting and important findings of our study is that exposure of female Ae. aegypti mosquitoes to nanoceria via blood meals significantly reduced egg clutches apparently via arresting oocyte growth, thereby interfering with the ultimate development and production of eggs. Thus, this study reveals until-now-unappreciated impacts of nanoceria exposure on Ae. aegypti mosquitoes and helps inform how these kinds of agents can be potentially deployed in control strategies.

Nanoscale cerium oxide surface chemistry has been studied intensively due to its pronounced activity in various catalytic applications. The material’s surface reactivity is generally attributed to oxygen vacancy density and the facile inter-conversion between Ce3+ and Ce4+ redox states. However, experimental and theoretical investigations suggest a more intricate surface chemistry. In this study, cerium oxide nanoparticles (CNPs) were modified with high-valence oxo-anions to modulate surface electronic structure and chemical interactions with medically-relevant analytes. Changes to the surface chemical environment were assessed via x-ray photoelectron spectroscopy (XPS) (e.g. binding energy shifts; peak number and character), while charge transfer properties were characterized through electrochemical impedance spectroscopy and circuit fitting (following ligand@particle electrophoretic deposition in dH2O onto glassy carbon electrodes, GCE). Further, the influence of vacancy density and ligand interaction was characterized via doping Sm3+ into CNPs in varying dopant fractions (0-15 mol%; oxygen vacancy concentration increases linearly with Sm3+ concentration). From here, ligand@CNP-modified GCEs were assessed for amperometric (via chronoamperometry) and voltametric (via square-wave voltammetry) sensitivity towards catechols, ascorbic acid, and glucose in phosphate buffered saline. Time of response and selectivity (in presence of structural chemical analogues) were also assessed in similar conditions. Relative sensitivities/performances were analyzed and compared in relation to XPS and electroanalysis trends/characters for future design of optimized biosensor platforms.

Cerium oxide nanomaterials are known to absorb ionizing radiation energy, as well as to neutralize free radicals in solution, by undergoing redox changes. We, therefore, proposed that ceria nanoparticles could be used in biomedical applications as an injectable, radio-protectant material. In this study, we examine the effectiveness of engineered nanoparticles in protecting germ cells from the damaging effects of irradiation-induced cell death, in vivo. C57BL/6J male mice were used as a model and irradiation was localized to the scrotal region at 2.5, 5, and/or 10 Gy intensities. Ceria nanoparticles were introduced as 100 μL injections at 100 nM and 100 μM via tail vein injections, weekly, for one month. Following this, the animals were sacrificed and their organs (heart, brain, kidneys) were harvested. Tissues were fixed, sectioned, and stained for instances of cell death, DNA damage (TUNEL assay), and ROS (nitro-tyrosine evolution). Tissues from mice treated with ceria nanoparticles showed significantly less (∼13% decrease; *P < 0.05) tissue damage (per immunohistochemistry) over controls at up to 5 Gy radiation. DNA damage and ROS also decrease substantially with ceria treatment, confirming ceria's capacity as an injectable, radio-protectant material. The study also highlights the ability of ceria nanoparticles to protect cells/tissues from both direct and indirect effects of ionizing radiation.

Cerium oxide (ceria) nanoparticles (CNPs) were synthesized in poly(ethylene glycol)s (PEGs) of different molecular weights (MWs; 300, 600, 1500, 3000, 4000, and 6000 Da) with water as a cosolvent, and changes in physicochemical properties, especially morphology and size, were monitored as a function of time. High-resolution transmission electron microscopy (HRTEM) was performed for all solutions and revealed octahedral, star morphologies for CNPs coated with 1500 MW PEG. Raman and FTIR spectroscopy, HRTEM images, conductivity, and electrophoretic mobility imply the self-assembly of small spherical particles to octahedral, star-shaped particles by means of a fractal assembly method. Dynamic light scattering measures were used to create an empirical growth model of the observed octahedral self-assembly. It was also determined that PEG polymer chain lengths and age-dependent redox activities of CNPs limit or allow this assembly owing to molecular-weight-dependent physicochemical properties. This study highlights the significance of ageing on solution-based nanoparticles and its implications in the use of nanoparticles over long periods of time. As PEG-ylated nanoparticles have found extensive use in biomedical applications, we have tested the aged particles in vitro for toxicity.

Nanoporous gold (NPG) has remarkable catalytic activity and biocompatibility and could potentially be used in biomedical devices. Herein, we have assessed the long term effects of biofouling on NPG interface. Nanoporoes (25 nm) in gold electrode are fabricated using a de-alloying treatment resulting in an 18 fold increase in surface area as compared to the planar gold. The effects of biofouling on the planar gold interface were evidenced by the rapid decrease in faradaic current to 55% in just eight minutes of incubation in 2 mg ml−1 of bovine serum albumin (BSA). On the other hand NPG showed barely any decline in the peak current when incubated in a similar biofouling solution. NPG upon incubation in a solution of higher concentration of BSA showed immediate peak current degradation which was subsequently recovered when the electrode was left idle in the biofouling solution. For instance, the peak current regenerated from (60% to 80%) when left idle for 60 minutes in 16 mg ml−1 of BSA solution. The regeneration mechanism indicated that even after long term incubation in the biofouling solution, the accumulated organic layer on its interface is not impervious and allows the diffusion of small analytes molecules. Thereby, NPG could be used in biomedical devices such as biosensor or drug reservoir.

In this work, we tested our hypothesis that surface chemistry and antioxidant properties of cerium nanoparticles (CNPs) are affected by presence of counterions. We first employed various precursor cerium (III) (Ce(III)) salts with different counterions (acetate, nitrate, chloride, sulfate) to synthesize CNPs following the same wet chemical methodology. Electron spin resonance (ESR) studies provided evidence for the formation of radicals from counterions (e.g., NO3•2− from reduction of NO3− in CNPs synthesized from Ce(III) nitrate). Physicochemical properties of these CNPs, e.g., dispersion stability, hydrodynamic size, signature surface chemistry, SOD-mimetic activity, and oxidation potentials were found to be significantly affected by the anions of the precursor salts. CNPs synthesized from Ce(III) nitrate and Ce(III) chloride exhibited higher extent of SOD-mimetic activities. Therefore, these CNPs were studied extensively employing in-situ UV-Visible spectroelectrochemistry and changing the counterion concentrations affected the oxidation potentials of these CNPs. Thus, the physicochemical and antioxidant properties of CNPs can be modulated by anions of the precursor. Furthermore, our ESR studies present evidence of the formation of guanine cation radical (G•+) in 5′-dGMP via UV-photoionization at 77 K in the presence of CNPs synthesized from Ce(III) nitrate and chloride and CNPs act as the scavenger of radiation-produced electrons.

A philosophical shift has occurred in the field of biomedical sciences from treatment of late-stage disease symptoms to early detection and prevention. Ceria nanoparticles (CNPs) have been demonstrated to neutralize free radical chemical species associated with many life-threatening disease states such as cancers and neurodegenerative diseases by undergoing redox changes (Ce3+ ↔ Ce4+). Herein, we investigate the electrochemical response of multi-valent CNPs in presence of hydrogen peroxide and demonstrate an enzyme-free CNP-based biosensor capable of ultra-low (limit of quantitation: 0.1 pM) detection. Several preparations of CNPs with varying Ce3+:Ce4+ are produced and are analyzed by electrochemical methods. We find that an increasing magnitude of response in cyclic voltammetry and chronoamperometry correlates with increasing Ce4+ relative to Ce3+ and utilize this finding in the design of the sensor platform. The sensor retains sensitivity across a range of pH’s and temperatures, wherein enzyme-based sensors will not function, and in blood serum: reflecting selectivity and robustness as a potential implantable biomedical device.

Cerium oxide nanoparticles (CNPs) exhibit superoxide dismutase (SOD) and catalase mimetic activities. Therefore, based on its catalytic activities, CNPs can potentially be used to treat diseases associated with oxidative stress. The potency of CNPs can be hindered by ion interaction due to chemical modifications. The issue is that phosphate ions are relatively ubiquitous in all biological relevance medium and body fluid. Our ventures in this study were to understand the phosphate ion interaction and fabricate CNPs that are biocompatible and simultaneously retain their catalytic properties in the presence of phosphate ions. CNPs were coated with polyethylene glycol and dextran in order to enhance biocompatibility. A series of experiments determined that maximizing the preserved catalytic responses were highly dependent on the Ce3+:Ce4+. Results have shown that the particles engineered with higher concentrations of Ce4+ on the surface are more robust and retain catalytic activity post buffer exposure.

The application of cerium oxide nanoparticles (CNPs) for therapeutic purposes requires a stable dispersion of nanoparticles in a biological environment. The objective of this study is to tailor the properties of polyelectrolyte coated CNPs as a function of molecular weight to achieve a stable and catalytic active dispersion. The coating of CNPs with polyacrylic acid (PAA) has increased the dispersion stability of CNPs and enhanced the catalytic ability. The stability of PAA coating was analyzed using the change in the Gibbs free energy computed by the Langmuir adsorption model. The adsorption isotherms were determined using soft particle electrokinetics which overcomes the challenges presented by other techniques. The change in Gibbs free energy was highest for CNPs coated with PAA of 250 kg/mol indicating the most stable coating. The change in free energy for PAA of 100 kg/mol coated CNPs was 85% lower than the PAA of 250 kg/mol coated CNPs. This significant difference is caused by the strong adsorption of PAA of 100 kg/mol on CNPs. Catalytic activity of PAA-CNPs is assessed by the catalase enzymatic mimetic activity of nanoparticles. The catalase activity was higher for PAA coated CNPs as compared to bare CNPs which indicated preferential adsorption of hydrogen peroxide induced by coating. This indicates that the catalase activity is also affected by the structure of the coating layer.

Correction for ‘Antioxidant properties of ALD grown nanoceria films with tunable valency’ by Ankur Gupta et al., Biomater. Sci., 2019, DOI: 10.1039/c9bm00397e.

This study reports the synthesis of a ultra-sensitive biosensor for free radical (hydrogen peroxide) and hypochlorous acid detection at the physiological level and below. The polyacrylonitrile derived glassy carbon electrode was modified with liquid exfoliated 2D MoS 2 nanoparticles. Biosensor works for wide range of potential and performs multi-role detection eliminating the use of specific compound dedicated electrodes.

It is well-established in research literature that ceria nanoparticles (CNPs) are able to undergo redox reaction with several oxygen-containing species in single or double electron transfers. The oxidase-mimetic ability of these particles, specifically, has found use in several biosensor devices. In this study we sought to characterize and optimize the use of ceria nanoparticles coated in polyethylene glycol (PEG) for use in biosensors. Specifically, molecular weight of adsorbed polymer was varied, particles were allowed to age in solution, and each solution was assayed for catalase activity. Interestingly, this study revealed that different polymer chain lengths of PEG influence self-assembly of particles in solution, thus varying oxidase activity.

Informatics is a new and flourishing sector in biomedical engineering with biosensors playing a crucial, central role. Self-Assembled monolayer (SAM) based biosensors constitute a large portion of these due to their simplistic design and broad application. Herein we present a cerium oxide nanoparticle (CNPs) functionalized SAM biosensor for amperometric reactive oxygen species (ROS) detection. SAM-based biosensors often times employ enzymes to detect analytes. These sensors are limited to particular pH, salt concentration, and temperature conditions specific to normal conditions for the enzyme. Operation outside these conditions can cause irreversible protein denature and loss of sensation. It is well established that CNPs has unique oxidase like activity.[1, 2] Therefore, by using inorganic CNPs, this sensor is able to operate at adverse conditions without loss of sensitivity. The inorganic material also prevents phase interactions which could result in bio-fouling. The presented sensor is able to detect extremely low concentrations for H2O2 and with high selectivity. Bare gold electrode was used as a substrate and coated with an SAM of mercaptododecanoic acid (MDDA), a well-established SAM polymer. The carboxylic terminus of MDDA was used for CNPs conjugation. Cyclic voltammetry and chronoamperometric testing was performed in phosphate-buffered saline and potassium hexacyanoferrate, a well-known redox couple. Hydrogen peroxide was infused in micromolar concentrations for sensing. Comparison to bare gold electrodes shows orders of magnitude greater sensitivity to [H2O2] and significantly more defined analyte selectivity. References: 1. Hirst, S.M., et al., Anti inflammatory Properties of Cerium Oxide Nanoparticles. Small, 2009. 5(24): p. 2848-2856. 2. Gaynor, J.D., et al., Enzyme-free Detection of Hydrogen Peroxide from Cerium Oxide Nanoparticles Immobilized on Poly (4-vinylpyridine) Self–Assembled Monolayers. J. Mater. Chem. B, 2013.

Within the scope of traumatic brain injury research, the implications of radical oxygen species (ROS) have been a primary interest. The ability to monitor these species cannot only provide a window into the progression of resultant pathology but also assist in therapeutic intervention by detailing the associated ROS insult experienced by the afflicted patient. Formation of protein plaques and aggregates is also associated with traumatic brain injury. These can form a passivation layer on the sensor’s surface leading to bio-fouling, thus limiting or even nullifying the sensitivity. The nano-scale ‘roughness’ of our nanoporous gold (NPG) electrode augments the effective surface area for conduction and is found resistant to bio-fouling. Likely, the proteins are excluded from entering pores due to the constriction of pore sizes, which significantly reduces the sites for protein deposition. NPG and plain gold electrode (PG) were tested in bovine serum albumin and beta amyloid to assess relative biofouling resistivity. The cyclic voltammetry (CV) from BSA incubation shows promise for NPG while PG experiences rapid surface saturation and loss of sensitivity (fig.1). CV was also performed in phosphate buffered saline (PBS) with a well-known redox couple of potassium hexacyanoferrate (HCF). Comparison between the CV measures for each electrode shows the increased conductivity for NPG. The results implicate the dual benefits of using the NPG for electrodes for increased sensitivity and resistance to bio-fouling.