Comparison of metal-based nanoparticles and nanowires: Solubility, reactivity, bioavailability and cellular toxicity

While the toxicity of metal-based nanoparticles (NP) has been investigated in an increasing number of studies, little is known about metal-based fibrous materials, so-called nanowires (NWs). Within the present study, the physico-chemical properties of particulate and fibrous nanomaterials based on Cu, CuO, Ni, and Ag as well as TiO$_{2}$ and CeO$_{2}$ NP were characterized and compared with respect to abiotic metal ion release in different physiologically relevant media as well as acellular reactivity. While none of the materials was soluble at neutral pH in artificial alveolar fluid (AAF), Cu, CuO, and Ni-based materials displayed distinct dissolution under the acidic conditions found in artificial lysosomal fluids (ALF and PSF). Subsequently, four different cell lines were applied to compare cytotoxicity as well as intracellular metal ion release in the cytoplasm and nucleus. Both cytotoxicity and bioavailability reflected the acellular dissolution rates in physiological lysosomal media (pH 4.5); only Ag-based materials showed no or very low acellular solubility, but pronounced intracellular bioavailability and cytotoxicity, leading to particularly high concentrations in the nucleus. In conclusion, in spite of some quantitative differences, the intracellular bioavailability as well as toxicity is mostly driven by the respective metal and is less modulated by the shape of the respective NP or NW

In-Vitro Application of Magnetic Hybrid Niosomes: Targeted siRNA-Delivery for Enhanced Breast Cancer Therapy

Even though the administration of chemotherapeutic agents such as erlotinib is clinically established for the treatment of breast cancer, its efficiency and the therapy outcome can be greatly improved using RNA interference (RNAi) mechanisms for a combinational therapy. However, the cellular uptake of bare small interfering RNA (siRNA) is insufficient and its fast degradation in the bloodstream leads to a lacking delivery and no suitable accumulation of siRNA inside the target tissues. To address these problems, non-ionic surfactant vesicles (niosomes) were used as a nanocarrier platform to encapsulate Lifeguard (LFG)-specific siRNA inside the hydrophilic core. A preceding entrapment of superparamagnetic iron-oxide nanoparticles (FexOy-NPs) inside the niosomal bilayer structure was achieved in order to enhance the cellular uptake via an external magnetic manipulation. After verifying a highly effective entrapment of the siRNA, the resulting hybrid niosomes were administered to BT-474 cells in a combinational therapy with either erlotinib or trastuzumab and monitored regarding the induced apoptosis. The obtained results demonstrated that the nanocarrier successfully caused a downregulation of the LFG gene in BT-474 cells, which led to an increased efficacy of the chemotherapeutics compared to plainly added siRNA. Especially the application of an external magnetic field enhanced the internalization of siRNA, therefore increasing the activation of apoptotic signaling pathways. Considering the improved therapy outcome as well as the high encapsulation efficiency, the formulated hybrid niosomes meet the requirements for a cost-effective commercialization and can be considered as a promising candidate for future siRNA delivery agents

Understanding the impact of more realistic low-dose, prolonged engineered nanomaterial exposure on genotoxicity using 3D models of the human liver

Background: With the continued integration of engineered nanomaterials (ENMs) into everyday applications, it is important to understand their potential for inducing adverse human health effects. However, standard in vitro hazard characterisation approaches suffer limitations for evaluating ENM and so it is imperative to determine these potential hazards under more physiologically relevant and realistic exposure scenarios in target organ systems, to minimise the necessity for in vivo testing. The aim of this study was to determine if acute (24 h) and prolonged (120 h) exposures to five ENMs (TiO2, ZnO, Ag, BaSO4 and CeO2) would have a significantly different toxicological outcome (cytotoxicity, (pro-)inflammatory and genotoxic response) upon 3D human HepG2 liver spheroids. In addition, this study evaluated whether a more realistic, prolonged fractionated and repeated ENM dosing regime induces a significantly different toxicity outcome in liver spheroids as compared to a single, bolus prolonged exposure. Results: Whilst it was found that the five ENMs did not impede liver functionality (e.g. albumin and urea production), induce cytotoxicity or an IL-8 (pro-)inflammatory response, all were found to cause significant genotoxicity following acute exposure. Most statistically significant genotoxic responses were not dose-dependent, with the exception of TiO2. Interestingly, the DNA damage effects observed following acute exposures, were not mirrored in the prolonged exposures, where only 0.2–5.0 μg/mL of ZnO ENMs were found to elicit significant (p ≤ 0.05) genotoxicity. When fractionated, repeated exposure regimes were performed with the test ENMs, no significant (p ≥ 0.05) difference was observed when compared to the single, bolus exposure regime. There was < 5.0% cytotoxicity observed across all exposures, and the mean difference in IL-8 cytokine release and genotoxicity between exposure regimes was 3.425 pg/mL and 0.181%, respectively. Conclusion: In conclusion, whilst there was no difference between a single, bolus or fractionated, repeated ENM prolonged exposure regimes upon the toxicological output of 3D HepG2 liver spheroids, there was a difference between acute and prolonged exposures. This study highlights the importance of evaluating more realistic ENM exposures, thereby providing a future in vitro approach to better support ENM hazard assessment in a routine and easily accessible manner.[Figure not available: see fulltext.

Nanomedicine for drug delivery in South Africa: a protocol for systematic review

Background: The emergence of nanomedicine in the past decade has changed the landscape of disease diagnosis and treatment. Nanomedicine makes use of nanostructures for applications in different fields of medicine, including drug delivery, biosensors, neuro-electronic interfaces, in vivo imaging, and cell-specific molecular interactions. Despite its relative infancy, nanomedicine has generated a significant body of research as evidenced by peer reviewed literature and several patents. This proposed systematic review will focus specifically on drug delivery systems in which nanoparticles are used to enhance the pharmacological and therapeutic properties of drugs. The strength of nanoparticulate drug delivery systems is their ability to alter the pharmacokinetics and bio-distribution of drugs. Globally, the discourse on nanomedicine is dominated by research being done in the developed countries of Europe and in the United States of America. Less attention has been given to the applications of nanomedicine in developing countries, particularly Africa. There is dearth of information on the applications of nanomedicine in terms of drug delivery with particular reference to which diseases are being targeted generally in Africa. The review will describe the specific diseases that are being targeted and the progress being made in South Africa, with a view to determining whether the applications of nanomedicine are being appropriated to address the context-specific challenges in this country or if they mimic what is being done globally. Methods: Keywords related to nanomedicine and drug delivery will be combined to build a search strategy for each of the following databases: PubMed, Cochrane Library (including Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews, Cochrane Methodology Register), Google Scholar, NHS Health Technology Assessment Database and Web of Science. We will also check reference lists of included studies for other eligible reports and search unpublished data. To ensure that the search is comprehensive, grey literature will be searched extensively. Literature to be included will have nanomedicine in drug delivery as the primary application and report on the specific diseases that are targeted in South Africa. Two authors will independently screen the search output, select studies and extract data; discrepancies will be resolved by consensus and discussion. When no consensus is reached, the third author will be consulted. Discussion: The systematic review will inform the government, policy-makers, investors, health professionals, scientists, and engineers about the applications of nanomedicine in drug delivery. In particular, it will identify the diseases targeted by the application of nanomedicine for drug delivery and the progress being made in South Africa as the disease burden of this country differs from that of developed countries where nanomedicine has been widely used for drug delivery. Systematic review registration PROSPERO CRD4201705738

Oxidative stress parameters in patients with slow coronary flow [Meeting Abstract]

31st Congress of the Federation-of-European-Biochemical-Societies (FEBS) -- JUN 24-29, 2006 -- Istanbul, TURKEYAbstract Not AvailableFederat European Biochem So

Oxidative stress parameters in patients with slow coronary flow

Introduction: We investigated the probable role of free-radical damage in the pathogenesis of slow coronary flow (SCF) by using oxidative stress parameters. Methods: Sixty-four patients with angiographically proven SCF and 63 patients with normal coronary flow (NCF) pattern with similar risk profiles were enrolled in this study. We measured erythrocyte superoxide dismutase (SOD), reduced glutathione (GSH), serum malondialdehyde (MDA), catalase and myeloperoxidase (MPO) levels in all subjects. Results: There were statistically significant differences in the levels of erythrocyte SOD, GSH and serum MDA between the 2 groups. Serum MDA (P = 0.003) and erythrocyte SOD levels (P = 0.0001) were increased in the SCF group. The level of erythrocyte GSH (P = 0.010) was lower in patients with SCF. There were no differences between the groups' serum catalase (P = 0.682) and MPO levels (P = 0.070). Conclusion: Our data showed that in patients with SCF, serum MDA and erythrocyte SOD levels were increased while erythrocyte GSH levels were decreased significantly, compared with NCF patients. These results indicate that free-radical damage may play a role in the pathogenesis of SCF. © Springer Healthcare Communications 2008