Craig J. Neal

Controlling the surface chemistry of cerium oxide nanoparticles for biological applications

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.

Electrochemical study of nanoporous gold revealing anti-biofouling properties

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.

Understanding the adsorption interface of polyelectrolyte coating on redox active nanoparticles using soft particle electrokinetics and its biological activity.

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.

Picomolar Detection of Hydrogen Peroxide using Enzyme-free Inorganic Nanoparticle-based Sensor

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.

Engineered nanoceria cytoprotection in vivo: mitigation of reactive oxygen species and double-stranded DNA breakage due to radiation exposure

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 cerias 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.

2D MoS 2 /glassy carbon based electrochemical sensor for pico-molar detection of hydrogen peroxide and hypochlorous acid

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 MoS2 nanoparticles. Biosensor works for wide range of potential and performs multi-role detection eliminating the use of specific compound dedicated electrodes.