Nanotoxicity of polyelectrolyte-functionalized titania nanoparticles towards microalgae and yeast: Role of the particle concentration, size and surface charge

We studied the nanotoxicity of titania nanoparticles (TiO₂NPs) of various hydrodynamic diameters and crystallite sizes towards C. reinhardtii microalgae and S. cerevisiae (yeast) upon illumination with UV and visible light. The cell viability was assessed for a range of nanoparticle concentrations and incubation times. We found that bare TiO₂NPs affect the C. reinhardtii cell viability at much lower particle concentrations than for yeast. We observed an increase of the TiO₂NPs toxicity upon illumination with UV light compared with that in dark conditions due to the oxidative stress of the produced reactive oxygen species. We also found an increased TiO₂NPs nanotoxicity upon illumination with visible light which indicates that they may also interfere with the microalgae's photosynthetic system leading to decreased chlorophyll content upon exposure to TiO₂NPs. The results indicate that the larger the hydrodynamic diameter of the TiO₂NPs the lower is their nanotoxicity, with anatase TiO₂NPs generally being more toxic than rutile TiO₂NPs. We also prepared a range of polyelectrolyte-coated TiO₂NPs using a layer by-layer method and studied their nanotoxicity towards yeast and microalgae. We found that the toxicity of the coated TiO₂NPs changes with their surface charge. TiO₂NPs coated with cationic polyelectrolyte as an outer layer exhibit much higher nanotoxicity than the ones with an outer layer of anionic polyelectrolyte. TEM images of sectioned microalgae and yeast cells exposed to different polyelectrolyte-coated TiO₂NPs confirmed the formation of a significant build-up of nanoparticles on the cell surface for bare and cationic polyelectrolyte-coated TiO₂NPs. The effect comes from the increased adhesion of cationic nanoparticles to the cell walls. Significantly, coating the TiO₂NPs with anionic polyelectrolyte as an outer layer led to a reduced adhesion and much lower nanotoxicity due to electrostatic repulsion with the cell walls. This suggest a new way of making cationic TiO₂NPs safer for use in different formulations by pre-coating them with anionic polyelectrolytes. The results of this study give important insights into the various factors controlling the nanotoxicity of TiO₂NPs

A Bayesian regression tree approach to identify the effect of nanoparticles' properties on toxicity profiles

We introduce a Bayesian multiple regression tree model to characterize relationships between physico-chemical properties of nanoparticles and their in-vitro toxicity over multiple doses and times of exposure. Unlike conventional models that rely on data summaries, our model solves the low sample size issue and avoids arbitrary loss of information by combining all measurements from a general exposure experiment across doses, times of exposure, and replicates. The proposed technique integrates Bayesian trees for modeling threshold effects and interactions, and penalized B-splines for dose- and time-response surface smoothing. The resulting posterior distribution is sampled by Markov Chain Monte Carlo. This method allows for inference on a number of quantities of potential interest to substantive nanotoxicology, such as the importance of physico-chemical properties and their marginal effect on toxicity. We illustrate the application of our method to the analysis of a library of 24 nano metal oxides.Comment: Published at http://dx.doi.org/10.1214/14-AOAS797 in the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

The impact of species and cell type on the nanosafety profile of iron oxide nanoparticles in neural cells

Background: While nanotechnology is advancing rapidly, nanosafety tends to lag behind since general mechanistic insights into cell-nanoparticle (NP) interactions remain rare. To tackle this issue, standardization of nanosafety assessment is imperative. In this regard, we believe that the cell type selection should not be overlooked since the applicability of cell lines could be questioned given their altered phenotype. Hence, we evaluated the impact of the cell type on in vitro nanosafety evaluations in a human and murine neuroblastoma cell line, neural progenitor cell line and in neural stem cells. Acute toxicity was evaluated for gold, silver and iron oxide (IO) NPs, and the latter were additionally subjected to a multiparametric analysis to assess sublethal effects. Results: The stem cells and murine neuroblastoma cell line respectively showed most and least acute cytotoxicity. Using high content imaging, we observed cell type-and species-specific responses to the IONPs on the level of reactive oxygen species production, calcium homeostasis, mitochondrial integrity and cell morphology, indicating that cellular homeostasis is impaired in distinct ways. Conclusions: Our data reveal cell type-specific toxicity profiles and demonstrate that a single cell line or toxicity end point will not provide sufficient information on in vitro nanosafety. We propose to identify a set of standard cell lines for screening purposes and to select cell types for detailed nanosafety studies based on the intended application and/or expected exposure

Controlling the nanotoxicity of polyelectrolyte-functionalized titania nanoparticles

This study gives important insights of the various factors controlling the nanotoxicity of titania nanoparticles (TiO2NPs). We studied the nanotoxicity of TiO2NPs of various hydrodynamic diameters and crystallite sizes on C. Reinhardtii (microalgae) and S. cerevisiae (yeast) upon illumination with UV/visible light [1]. The cell viability was assessed for a range of nanoparticle concentrations and incubation times. Bare TiO2NPs affect the microalgae viability at much lower particle concentrations than for yeast. We also found an increased nanotoxicity upon illumination with visible light which indicates that they may also interfere with the microalgae photosynthetic system leading to decreased chlorophyll content upon exposure to TiO2NPs. The results indicate that the larger the hydrodynamic diameter of the TiO2NPs the lower is their nanotoxicity, with anatase TiO2NPs generally being more cytotoxic than rutile TiO2NPs. We also prepared a range of polyelectrolyte-coated TiO2NPs using the layer by-layer method and studied their nanotoxicity on yeast and microalgae. The toxicity of the coated TiO2NPs alternates with their surface charge. TiO2NPs coated with cationic polyelectrolyte as an outer layer exhibit much higher nanotoxicity than the ones with an outer layer of anionic polyelectrolyte. TEM images of sectioned microalgae and yeast cells exposed to different polyelectrolyte-coated TiO2NPs confirmed the formation of a significant build-up of nanoparticles on the cell surface for bare- and cationic polyelectrolyte-coated TiO2NPs. The effect is coming from the increased adhesion of cationic nanoparticles to the cell walls. Significantly, coating the TiO2NPs with an anionic polyelectrolyte as an outer layer led to a reduced adhesion and much lower nanotoxicity due to electrostatic repulsion with the cell walls. This suggest a new way of making the TiO2NPs potentially safer for use in different formulations by pre-coating them with anionic polyelectrolytes. Please click Additional Files below to see the full abstract

Sizing nanomatter in biological fluids by fluorescence single particle tracking

Accurate sizing of nanoparticles in biological media is important for drug delivery and biomedical imaging applications since size directly influences the nanoparticle processing and nanotoxicity in vivo. Using fluorescence single particle cracking we have succeeded for the first time in following the aggregation of drug delivery nanoparticles in real time in undiluted whole blood. We demonstrate that, by using a suitable surface functionalization, nanoparticle aggregation in the blood circulation is prevented to a large extent

Nanoinformatics: developing new computing applications for nanomedicine

Nanoinformatics has recently emerged to address the need of computing applications at the nano level. In this regard, the authors have participated in various initiatives to identify its concepts, foundations and challenges. While nanomaterials open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treatment of diseases. In this paper, we analyze the different aspects of nanoinformatics and suggest five research topics to help catalyze new research and development in the area, particularly focused on nanomedicine. We also encompass the use of informatics to further the biological and clinical applications of basic research in nanoscience and nanotechnology, and the related concept of an extended ?nanotype? to coalesce information related to nanoparticles. We suggest how nanoinformatics could accelerate developments in nanomedicine, similarly to what happened with the Human Genome and other -omics projects, on issues like exchanging modeling and simulation methods and tools, linking toxicity information to clinical and personal databases or developing new approaches for scientific ontologies, among many others

Cytotoxicity in the Age of Nano: The Role of Fourth Period Transition Metal Oxide Nanoparticle Physicochemical Properties

A clear understanding of physicochemical factors governing nanoparticle toxicity is still in its infancy. We used a systematic approach to delineate physicochemical properties of nanoparticles that govern cytotoxicity. The cytotoxicity of fourth period metal oxide nanoparticles (NPs): TiO2, Cr2O3, Mn2O3, Fe2O3, NiO, CuO, and ZnO increases with the atomic number of the transition metal oxide. This trend was not cell-type specific, as observed in non-transformed human lung cells (BEAS-2B) and human bronchoalveolar carcinoma-derived cells (A549). Addition of NPs to the cell culture medium did not significantly alter pH. Physiochemical properties were assessed to discover the determinants of cytotoxicity: (1) point-of-zero charge (PZC) (i.e., isoelectric point) described the surface charge of NPs in cytosolic and lysosomal compartments; (2) relative number of available binding sites on the NP surface quantified by X-ray photoelectron spectroscopy was used to estimate the probability of biomolecular interactions on the particle surface; (3) band-gap energy measurements to predict electron abstraction from NPs which might lead to oxidative stress and subsequent cell death; and (4) ion dissolution. Our results indicate that cytotoxicity is a function of particle surface charge, the relative number of available surface binding sites, and metal ion dissolution from NPs. These findings provide a physicochemical basis for both risk assessment and the design of safer nanomaterials