Silver nanoparticle toxicity in Drosophila: size does matter

Deborah J Gorth1, David M Rand2, Thomas J Webster11School of Engineering, 2Department of Ecology and Evolutionary Biology, Brown University, Providence, RI, USABackground: Consumer nanotechnology is a growing industry. Silver nanoparticles are the most common nanomaterial added to commercially available products, so understanding the influence that size has on toxicity is integral to the safe use of these new products. This study examined the influence of silver particle size on Drosophila egg development by comparing the toxicity of both nanoscale and conventional-sized silver particles.Methods: The toxicity assays were conducted by exposing Drosophila eggs to particle concentrations ranging from 10 ppm to 100 ppm of silver. Size, chemistry, and agglomeration of the silver particles were evaluated using transmission electron microscopy, X-ray photoelectron spectroscopy, and dynamic light scattering.Results: This analysis confirmed individual silver particle sizes in the ranges of 20–30 nm, 100 nm, and 500–1200 nm, with similar chemistry. Dynamic light scattering and transmission electron microscope data also indicated agglomeration in water, with the transmission electron microscopic images showing individual particles in the correct size range, but the dynamic light scattering z-average sizes of the silver nanoparticles were 782 ± 379 nm for the 20–30 nm silver nanoparticles, 693 ± 114 nm for the 100 nm silver nanoparticles, and 508 ± 32 nm for the 500–1200 nm silver particles. Most importantly, here we show significantly more Drosophila egg toxicity when exposed to larger, nonnanometer silver particles. Upon exposure to silver nanoparticles sized 20–30 nm, Drosophila eggs did not exhibit a statistically significant (P < 0.05) decrease in their likelihood to pupate, but eggs exposed to larger silver particles (500–1200 nm) were 91% ± 18% less likely to pupate. Exposure to silver nanoparticles reduced the percentage of pupae able to emerge as adults. At 10 ppm of silver particle exposure, only 57% ± 48% of the pupae exposed to 20–30 nm silver particles became adults, whereas 89% ± 25% of the control group became adults, and 94% ± 52% and 91% ± 19% of the 500–1200 nm and 100 nm group, respectively, reached adulthood.Conclusion: This research provides evidence that nanoscale silver particles (<100 nm) are less toxic to Drosophila eggs than silver particles of conventional (>100 nm) size.Keywords: Drosophila, silver, nanoparticle, toxicity&nbsp

Dextran and Polymer Polyethylene Glycol (PEG) Coating Reduce Both 5 and 30 nm Iron Oxide Nanoparticle Cytotoxicity in 2D and 3D Cell Culture

Superparamagnetic iron oxide nanoparticles are widely used in biomedical applications, yet questions remain regarding the effect of nanoparticle size and coating on nanoparticle cytotoxicity. In this study, porcine aortic endothelial cells were exposed to 5 and 30 nm diameter iron oxide nanoparticles coated with either the polysaccharide, dextran, or the polymer polyethylene glycol (PEG). Nanoparticle uptake, cytotoxicity, reactive oxygen species (ROS) formation, and cell morphology changes were measured. Endothelial cells took up nanoparticles of all sizes and coatings in a dose dependent manner, and intracellular nanoparticles remained clustered in cytoplasmic vacuoles. Bare nanoparticles in both sizes induced a more than 6 fold increase in cell death at the highest concentration (0.5 mg/mL) and led to significant cell elongation, whereas cell viability and morphology remained constant with coated nanoparticles. While bare 30 nm nanoparticles induced significant ROS formation, neither 5 nm nanoparticles (bare or coated) nor 30 nm coated nanoparticles changed ROS levels. Furthermore, nanoparticles were more toxic at lower concentrations when cells were cultured within 3D gels. These results indicate that both dextran and PEG coatings reduce nanoparticle cytotoxicity, however different mechanisms may be important for different size nanoparticles

Biocompatibility of Common Implantable Sensor Materials in a Tumor Xenograft Model

Real-time monitoring of tumor microenvironment parameters using an implanted biosensor could provide valuable information on the dynamic nature of a tumor's biology and its response to treatment. However, following implantation biosensors may lose functionality due to biofouling caused by the foreign body response (FBR). This study developed a novel tumor xenograft model to evaluate the potential of six biomaterials (silicon dioxide, silicon nitride, Parylene-C, Nafion, biocompatible EPOTEK epoxy resin, and platinum) to trigger a FBR when implanted into a solid tumor. Biomaterials were chosen based on their use in the construction of a novel biosensor, designed to measure spatial and temporal changes in intra-tumoral O2 , and pH. None of the biomaterials had any detrimental effect on tumor growth or body weight of the murine host. Immunohistochemistry showed no significant changes in tumor necrosis, hypoxic cell number, proliferation, apoptosis, immune cell infiltration, or collagen deposition. The absence of biofouling supports the use of these materials in biosensors; future investigations in preclinical cancer models are required, with a view to eventual applications in humans. To our knowledge this is the first documented investigation of the effects of modern biomaterials, used in the production of implantable sensors, on tumor tissue after implantation. © 2018 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B, 2018

Dissolution behaviour of silicon nitride coatings for joint replacements

In this study, the dissolution rate of SiNx coatings was investigated as a function of coating composition, in comparison to a cobalt chromium molybdenum alloy (CoCrMo) reference. SiNx coatings with N/Si ratios of 0.3, 0.8 and 1.1 were investigated. Electrochemical measurements were complemented with solution (inductively coupled plasma techniques) and surface analysis (vertical scanning interferometry and x-ray photoelectron spectroscopy). The dissolution rate of the SiNx coatings was evaluated to 0.2–1.4 nm/day, with a trend of lower dissolution rate with higher N/Si atomic ratio in the coating. The dissolution rates of the coatings were similar to or lower than that of CoCrMo (0.7–1.2 nm/day). The highest nitrogen containing coating showed mainly Si–N bonds in the bulk as well as at the surface and in the dissolution area. The lower nitrogen containing coatings showed Si–N and/or Si–Si bonds in the bulk and an increased formation of Si–O bonds at the surface as well as in the dissolution area. The SiNx coatings reduced the metal ion release from the substrate. The possibility to tune the dissolution rate and the ability to prevent release of metal ions encourage further studies on SiNx coatings for joint replacements

Advancing cell therapies for intervertebral disc regeneration from the lab to the clinic: recommendations of the ORS spine section

Intervertebral disc degeneration is strongly associated with chronic low back pain, a leading cause of disability worldwide. Current back pain treatment approaches (both surgical and conservative) are limited to addressing symptoms, not necessarily the root cause. Not surprisingly therefore, long‐term efficacy of most approaches is poor. Cell‐based disc regeneration strategies have shown promise in preclinical studies, and represent a relatively low‐risk, low‐cost, and durable therapeutic approach suitable for a potentially large patient population, thus making them attractive from both clinical and commercial standpoints. Despite such promise, no such therapies have been broadly adopted clinically. In this perspective we highlight primary obstacles and provide recommendations to help accelerate successful clinical translation of cell‐based disc regeneration therapies. The key areas addressed include: (a) Optimizing cell sources and delivery techniques; (b) Minimizing potential risks to patients; (c) Selecting physiologically and clinically relevant efficacy metrics; (d) Maximizing commercial potential; and (e) Recognizing the importance of multidisciplinary collaborations and engaging with clinicians from inception through to clinical trials

Comparison of hospitalized childhood patients with Rotavirus-associated gastroenteritis at the university hospital Innsbruck before and after the introduction of the universal rotavirus vaccination in Austria

Die Dissertation untersucht hospitalisierte Patienten in der Kinderklinik des Universitätsklinikum Innsbruck, die wegen einer rotaviren assoziierten Gastroenteritis hospitalisiert wurden. Der Untersuchungszeitraum war von Januar 2002 bis Dezmber 2012.Untersucht wurde die Hospitalisierungsrate, Hospitalisierungsdauer, Hospitalisierungsalter, die Schwere der Erkrankung sowie eine Änderung von nosokomialen und ambulanten Erwerb vor und nach Impfeinführung im Juli 2007.The dissertation examines hospitalized patients in the children's clinic of the University Medical Center Innsbruck who were hospitalized for rotavirus-associated gastroenteritis. The study period was from January 2002 to December 2012 and examined the hospitalization rate, length of hospitalization, age of hospitalization, the severity of the disease and a change in nosocomial and outpatient acquisition before and after the vaccination was introduced in July 2007