Guogang Ren

Characterisation of copper oxide nanoparticles for antimicrobial applications.

Copper oxide (CuO) nanoparticles were characterised and investigated with respect to potential antimicrobial applications. It was found that nanoscaled CuO, generated by thermal plasma technology, contains traces of pure Cu and Cu2O nanoparticles. Transmission electron microscopy (TEM) demonstrated particle sizes in the range 20-95 nm. TEM energy dispersive spectroscopy gave the ratio of copper to oxygen elements as 54.18% to 45.26%. The mean surface area was determined as 15.69 m(2)/g by Brunau-Emmet-Teller (BET) analysis. CuO nanoparticles in suspension showed activity against a range of bacterial pathogens, including meticillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli, with minimum bactericidal concentrations (MBCs) ranging from 100 microg/mL to 5000 microg/mL. The ability of CuO nanoparticles to reduce bacterial populations to zero was enhanced in the presence of sub-MBC concentrations of silver nanoparticles. Studies of CuO nanoparticles incorporated into polymers suggest release of ions may be required for optimum killing.

A review of nanoparticle functionality and toxicity on the central nervous system

Although nanoparticles have tremendous potential for a host of applications, their adverse effects on living cells have raised serious concerns recently for their use in the healthcare and consumer sectors. As regards the central nervous system (CNS), research data on nanoparticle interaction with neurons has provided evidence of both negative and positive effects. Maximal application dosage of nanoparticles in materials to provide applications such as antibacterial and antiviral functions is approximately 0.1–1.0 wt%. This concentration can be converted into a liquid phase release rate (leaching rate) depending upon the host or base materials used. For example, nanoparticulate silver (Ag) or copper oxide (CuO)-filled epoxy resin demonstrates much reduced release of the metal ions (Ag+ or Cu2+) into their surrounding environment unless they are mechanically removed or aggravated. Subsequent to leaching effects and entry into living systems, nanoparticles can also cross through many other barriers, such as skin and the blood–brain barrier (BBB), and may also reach bodily organs. In such cases, their concentration or dosage in body fluids is considered to be well below the maximum drug toxicity test limit (10−5 g ml−1) as determined in artificial cerebrospinal solution. As this is a rapidly evolving area and the use of such materials will continue to mature, so will their exposure to members of society. Hence, neurologists have equal interests in nanoparticle effects (positive functionality and negative toxicity) on human neuronal cells within the CNS, where the current research in this field will be highlighted and reviewed.

Oxidative stress and apoptosis induced by nanosized titanium dioxide in PC12 cells.

The nanosized titanium dioxide (nano-TiO2) is produced abundantly and used widely in the chemical, electrical/electronic and energy industries because of its special photovoltaic and photocatalytic activities. Past reports have shown that the nano-TiO2 can enter into the human body through different routes such as inhalation, ingestion, dermal penetration and injection. The effects of nano-TiO2 on different organs are currently being investigated and the concerns on its large scale applications such as sunscreen, etc. indeed become more interesting for us to investigate and to find the possible right answers for right doses for a safer application. In this research, the cytotoxicity of the nano-TiO2 was investigated in PC12 cells, a cell line used as a model in vitro for the brain neurons research. While the PC12 cells were treated with different concentrations of nano-TiO2 (1, 10, 50 and 100 microg/ml), the viability of cells was significantly decreased in the periods of 6, 12, 24 and 48 h, showing a significant dose effect and time-dependent manner. Meanwhile, the flow cytometric assay gave indication that the nano-TiO2 induced intracellular accumulation of reactive oxygen species (ROS) and the apoptosis of PC12 cells with the increasing concentration of nano-TiO2. Interestingly, pretreatment of N-(mercaptopropionyl)-glycine (N-MPG), known as a type of ROS scavenger formulations, could somehow inhibit PC12 apoptosis induced by the nano-TiO2. These results might have revealed a key mechanism in PC12 apoptosis under the effect of the nano-TiO2 solutions.

Influences of nanoparticle zinc oxide on acutely isolated rat hippocampal CA3 pyramidal neurons

The effects of zinc oxide nanoparticles (nano-ZnO) on the properties of voltage-dependent sodium, potassium currents and evoked action potentials were studied in acutely isolated rat hippocampal CA3 pyramidal neurons at postnatal ages of 10-14 days rats using the whole-cell patch-clamp technique. The results indicated that: (1) in the present of final concentration of 10(-4)g/ml nano-ZnO, the current-voltage curve of sodium current (I(Na)) was decreased, and the peak amplitudes of I(Na) were increased considerably from -50 to +20mV (p<0.05). Meanwhile, the inactivation and the recovery from inactivation of I(Na) were also promoted by the nano-ZnO solution (10(-4)g/ml) (p<0.01). However, the steady-state activation curve of I(Na) was not shifted by the nano-ZnO. (2) The amplitudes of transient outward potassium current (I(A)) were increased by the nano-ZnO solution (10(-4)g/ml), while the current-voltage curve of delayed rectifier potassium current (I(K)) was significantly increased from +20 to +90mV (p<0.05). However, it is apparent that the nano-ZnO solution did not shift the steady-state activation curve of I(A) and I(K), and neither had significant effects on the inactivation and the recovery from inactivation of I(A). (3) Peak amplitude and overshoot of the evoked single action potential were increased and half-width was diminished in the presence of the 10(-4)g/ml nano-ZnO solution (p<0.05). Simultaneously, a prolonged depolarizing current injection enhanced (p<0.05) repetitive firing evoked firing rate. These results suggested that 10(-4)g/ml nano-ZnO solution can lead to an enhancement in the current amplitudes of I(Na) and I(K) by increasing the opening number of sodium channels, delaying rectifier potassium channels, and enhancing the excitability of neurons, which lead to Na(+) influx and the accumulation of intracellular Na(+), as well as K(+) efflux plus the loss of cytoplasmic K(+). These may disturb the ionic homeostasis and the physiological functions of neurons.

Antimicrobial activity of nanoparticulate metal oxides against peri-implantitis pathogens

Dental plaque accumulation may result in peri-implantitis, an inflammatory process causing loss of supporting bone that may lead to dental implant failure. The antimicrobial activities of six metal and metal oxide nanoparticles and two of their composites against bacterial pathogens associated with peri-implantitis were examined under anaerobic conditions. The activities of nanoparticles of silver (Ag), cuprous oxide (Cu(2)O), cupric oxide (CuO), zinc oxide (ZnO), titanium dioxide (TiO(2)), tungsten oxide (WO(3)), Ag+CuO composite and Ag+ZnO composite were assessed by minimum inhibitory (bacteriostatic) concentration (MIC) and minimum bactericidal concentration (MBC) determination against Prevotella intermedia, Porphyromonas gingivalis, Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans. Time-kill assays were carried out to examine the dynamics of the antimicrobial activity with ZnO nanoparticles. MIC and MBC values were in the range of <100 μg/mL to 2500 μg/mL and <100 μg/mL to >2500 μg/mL, respectively. The activity of the nanoparticles tested in descending order was Ag>Ag+CuO>Cu(2)O>CuO>Ag+ZnO>ZnO>TiO(2)>WO(3). Time-kill assays with ZnO demonstrated a significant decrease in growth of all species tested within 4h, reaching 100% within 2h for P. gingivalis and within 3h for F. nucleatum and P. intermedia. Coating titanium surfaces of dental and orthopaedic implants with antimicrobial nanoparticles should lead to an increased rate of implant success.

Action potential changes associated with the inhibitory effects on voltage-gated sodium current of hippocampal CA1 neurons by silver nanoparticles.

Nano-sized materials are now being used in medicine, biotechnology, energy, and environmental technology. Although a wide and growing number of applications for nanomaterials exist, there are limited studies available on toxicity of nanoparticles for their human risk and environmental assessment. The aim of this study was to investigate the effects of silver nanoparticles (nano-Ag) on voltage-activated sodium currents in hippocampal CA1 neurons. Nano-Ag was tested at increasing concentrations (10(-6), 5 x 10(-6), 10(-5) g/ml). The research results showed that only nano-Ag (10(-5) g/ml) reduced the amplitude of voltage-gated sodium current (I(Na)). The nano-Ag particles produced a hyperpolarizing shift in the activation-voltage curve of I(Na) and also delayed the recovery of I(Na) from inactivation. Action potential properties and the pattern of repetitive firing were examined using whole cell current-clamp recordings. Peak amplitude and overshoot of the evoked single action potential were decreased and half-width was increased in the present of the 10(-5) g/ml nano-Ag solution, and the firing rate of repetitive firing had no change. The results suggest that nano-Ag may alter the action potential of hippocampal CA1 neurons by depressing voltage-gated sodium current.

The possible mechanism of silver nanoparticle impact on hippocampal synaptic plasticity and spatial cognition in rats

Silver nanoparticles (Ag-np) are very promising engineered nanomaterials which play an important role in the world biomedical, healthcare and in general nanotechnology applications. With the most impressive effect in antibacterial and many other broad-spectrum biotechnological advantages, Ag-np in real applications is still a controversial issue. This study investigated effects of the Ag-np on hippocampal synaptic plasticity and spatial cognition in rats and followed with the research on their possible mechanism. In this study, twenty-four adult male Wister rats were randomly divided into 3 groups: control group, low-dose group (Ag-np, 3 mg/kg) and high-dose group (Ag-np, 30 mg/kg). After two-week exposure to Ag-np through the nasal administration, Morris water maze (MWM) test was performed for the spatial cognition, followed by the long-term potentiation (LTP) recording and reactive oxygen species (ROS) detection in hippocampal homogenate. Results showed that compared with the control group, both LTP and MWM were abnormal in low-dose group and high-dose group. The quantity of ROS in hippocampal homogenate was increased significantly in low-dose group and high-dose group, which may be the reason of the neural damage caused by Ag-np.

Nano-zinc oxide damages spatial cognition capability via over-enhanced long-term potentiation in hippocampus of Wistar rats

This study focused on the effects of zinc oxide nanoparticles (nano-ZnO) on spatial learning and memory and synaptic plasticity in the hippocampus of young rats, and tried to interpret the underlying mechanism. Rats were randomly divided into four groups. Nano-ZnO and phosphate-buffered saline were administered in 4-week-old rats for 8 weeks. Subsequently, performance in Morris water maze (MWM) was determined, and then long-term potentiation (LTP) and depotentiation were measured in the perforant pathway to dentate gyrus (DG) in anesthetized rats. The data showed that, (1) in MWM, the escape latency was prolonged in the nano-ZnO group and, (2) LTP was significantly enhanced in the nano-ZnO group, while depotentiation was barely influenced in the DG region of the nano-ZnO group. This bidirectional effect on long-term synaptic plasticity broke the balance between stability and flexibility of cognition. The spatial learning and memory ability was attenuated by the alteration of synaptic plasticity in nano-ZnO-treated rats.

In vitro toxicity of multi-walled carbon nanotubes in C6 rat glioma cells.

The present study aimed to evaluate the potential toxicity and the general mechanism involved in multi-walled carbon nanotubes (MWCNT)-induced cytotoxicity in C6 rat glioma cell line. Two kinds of MWCNT, which were coded as MWCNT1 (measured 10-20 nm in diameter and 2 μm in average length) and MWCNT2 (measured 40-100 nm in diameter and 10 μm in average length), were used in this study. To elucidate the possible mechanisms of cytotoxicity induced by MWCNT, MTT assay and flow cytometry analysis for apoptosis and cell cycle, MDA and SOD assays for oxidative stress were quantitatively assessed. The exposure of C6 rat glioma cells to different sizes of two kinds of carbon nanotubes at concentrations between 25 and 400 μg/ml decreased the cell viability in a concentration- and time-dependent manner. The exposure of C6 rat glioma cells to MWCNT (200-400 μg/ml) resulted in a concentration dependent cell apoptosis and G1 cell cycle arrest, and increased the level of oxidative stress. Results demonstrate that smaller size of MWCNT seems to be more toxic than that of larger one. MWCNT-induced cytotoxicity in C6 cells is probably due to the increased oxidative stress.

Potential impact of nanotechnology on the control of infectious diseases

Summary Nanotechnology encompasses those technologies used to fabricate materials, including sphere, cubic and needle-like nanoscaled particles (approximately 5–100nm), and near-nanoscaled devices (up to micrometres). In comparison, mycoplasma are approximately 200nm in length, and a nanometre is 10−9 of a metre. The field of nanotechnology is experiencing rapid growth, with many and diverse potential applications being explored in the biomedical field, including the control of infectious diseases. Nanotechnology not only has the potential to offer improvements to current approaches for immunisation, drug design and delivery, diagnostics and cross-infection control, but is also unexpectedly delivering many new tools and capabilities.