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Food-grade titanium dioxide (E171) contains variable percentages of titanium dioxide (TiO2) nanoparticles (NPs), posing concerns for its potential effects on human and animal health. Despite many studies, the actual relationship between the physicochemical properties of E171 NPs and their interaction with biological targets is still far from clear. We evaluated the impact of acute E171 administration on invertebrate and vertebrate animals. In the nematode, Caenorhabditis elegans, the administration of up to 1.0 mg/mL of E171 did not affect the worm's viability and lifespan, but significantly impaired its pharyngeal function, reproduction, and development. We also investigated whether the intravenous administration of E171 in mice (at the dose of 6 mg/kg/body weight) could result in an acute over-absorption of filter organs. A significant increase of hepatic titanium concentration and the formation of microgranulomas were observed. Interstitial inflammation and parenchymal modification were found in the lungs, coupled with titanium accumulation. This was probably due to the propensity of TiO2 NPs to agglomerate, as demonstrated by transmission electron microscopy experiments showing that the incubation of E171 with serum promoted the formation of compact clusters. Overall, these data emphasize the actual risk for human and animal exposure to E171. [ABSTRACT FROM AUTHOR]

While substantial progress has been achieved in the design of more biocompatible nanoparticles (NP), detailed data are required on the precise interactions of NPs and their environment for more reliable interpretation of toxicity results. Therefore, this study aims to investigate the interaction of two quantum dots (QDs) of the same core material CdSe/ZnS coated with two different amphiphilic polymers, with two well-established mammalian cell lines representing possible sites of QD accumulation. Results are linked to either extracellular QD concentrations (given dose) or cellular QD levels (number of internalized particles). In this study, QD internalization, effects on cellular homeostasis, and consequent inflammatory and cytoskeletal alterations caused by these QDs were explored. Fluorescence imaging techniques, including; image-based flow cytometry, confocal microscopy and high-content imaging with the InCell analyzer were used in a multiparametric methodology to evaluate cell viability, induction of oxidative stress, mitochondrial health, cell cytoskeletal functionality and changes in cellular morphology. Gene expression arrays were also carried out on 168 key genes involved in the cytoskeletal architecture and inflammatory pathway accompanied with the analysis of focal adhesions as key markers for actin-mediated signaling. Our results show distinct differences between the PMA and PTMAEMA-stat-PLMA coated QDs, which could mainly be attributed to differences in their cellular uptake levels. The toxicity profiles of both QD types changed drastically depending on whether effects were expressed in terms of given dose or internalized particles. Both QDs triggered alterations to important but different genes, most remarkably the up-regulation of tumor suppression and necrosis genes and the down regulation of angiogenesis and metastasis genes at sub-cytotoxic concentrations of these QDs. [ABSTRACT FROM AUTHOR]

A homologous nanoparticle library was synthesized in which gold nanoparticles were coated with polyethylene glycol, whereby the diameter of the gold cores, as well as the thickness of the shell of polyethylene glycol, was varied. Basic physicochemical parameters of this two-dimensional nanoparticle library, such as size, ζ-potential, hydrophilicity, elasticity, and catalytic activity ,were determined. Cell uptake of selected nanoparticles with equal size yet varying thickness of the polymer shell and their effect on basic structural and functional cell parameters was determined. Data indicates that thinner, more hydrophilic coatings, combined with the partial functionalization with quaternary ammonium cations, result in a more efficient uptake, which relates to significant effects on structural and functional cell parameters. [ABSTRACT FROM AUTHOR]

We studied the physico-chemical properties (size, shape, zeta-potential), cellular internalization and toxicity of gold nanoparticles (NPs) stabilized with the most abundant mammalian protein, collagen. The properties of these gold NPs were compared to the same sized gold NPs coated with synthetic poly(isobutylene-alt-maleic anhydride) (PMA). Intracellular uptake and cytotoxicity were assessed in two cell lines (cervical carcinoma and lung adenocarcinoma cells) by employing inductively-coupled plasma-mass spectrometry (ICP-MS) analysis and a cell viability assay based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), respectively. We found that the collagen-coated gold NPs exhibit lower cytotoxicity, but higher uptake levels than PMA-coated gold NPs. These results demonstrate that the surface coating of Au NPs plays a decisive role in their biocompatibility. [ABSTRACT FROM AUTHOR]

The synthesis of polymer-coated gold nanoparticles with high colloidal stability is described, together with appropriate characterization techniques concerning the colloidal properties of the nanoparticles. Antibodies against vascular endothelial growth factor (VEGF) are conjugated to the surface of the nanoparticles. Antibody attachment is probed by different techniques, giving a guideline about the characterization of such conjugates. The effect of the nanoparticles on human adenocarcinoma alveolar basal epithelial cells (A549) and human umbilical vein endothelial cells (HUVECs) is probed in terms of internalization and viability assays. [ABSTRACT FROM AUTHOR]

Abstract: Colloidal semiconductor nanoparticles (quantum dots) have attracted a lot of interest in technological and biomedical research, given their potent fluorescent properties. However, the use of heavy-metal-containing nanoparticles remains an issue of debate. The possible toxic effects of quantum dots remain a hot research topic and several questions such as possible intracellular degradation of quantum dots and the effect thereof on both cell viability and particle functionality remain unresolved. In the present work, poly(methacrylic acid)-coated CdSe/ZnS quantum dots were synthesized and characterized, after which their effects on cultured cells were evaluated using a multiparametric setup. The data reveal that the quantum dots are taken up through endocytosis and when exposed to the low pH of the endosomal structures, they partially degrade and release cadmium ions, which lowers their fluorescence intensity and augments particle toxicity. Using the multiparametric method, the quantum dots were evaluated at non-toxic doses in terms of their ability to visualize labeled cells for longer time periods. The data revealed that comparing different particles in terms of their applied dose is challenging, likely due to difficulties in obtaining accurate nanoparticle concentrations, but evaluating particle toxicity in terms of their biological functionality enables an easy and straightforward comparison. [Copyright &y& Elsevier]

It is qualitatively demonstrated that the intracellular localization of particles depends on the way they are administered, their basic physicochemical properties, as well as on incubation time. For this purpose cells were exposed to fluorescently-labelled particles of different size under different exposure scenarios including incubation, microinjection, electroporation, and sonoporation. After co-exposure to cells the intracellular distribution of different particles was imaged with multicolor fluorescence microscopy. Qualitative co-localization analysis demonstrates, that different particles to which cells have been exposed in different ways did not automatically reside in the same compartment. As intracellular particle localization may influence potential toxic effects of particles on cells, studies attempting to unravel molecular mechanisms of toxicity should involve the determination of the intracellular particle distribution. [ABSTRACT FROM AUTHOR]

The use of nanotechnologies involving nano- and microparticles has increased tremendously in the recent past. There are various beneficial characteristics that make particles attractive for a wide range of technologies. However, colloidal particles on the other hand can potentially be harmful for humans and environment. Today, complete understanding of the interaction of colloidal particles with biological systems still remains a challenge. Indeed, their uptake, effects, and final cell cycle including their life span fate and degradation in biological systems are not fully understood. This is mainly due to the complexity of multiple parameters which need to be taken in consideration to perform the nanosafety research. Therefore, we will provide an overview of the common denominators and ideas to achieve universal metrics to assess their safety. The review discusses aspects including how biological media could change the physicochemical properties of colloids, how colloids are endocytosed by cells, how to distinguish between internalized versus membrane-attached colloids, possible correlation of cellular uptake of colloids with their physicochemical properties, and how the colloidal stability of colloids may vary upon cell internalization. In conclusion three main statements are given. First, in typically exposure scenarios only part of the colloids associated with cells are internalized while a significant part remain outside cells attached to their membrane. For quantitative uptake studies false positive counts in the form of only adherent but not internalized colloids have to be avoided. pH sensitive fluorophores attached to the colloids, which can discriminate between acidic endosomal/lysosomal and neutral extracellular environment around colloids offer a possible solution. Second, the metrics selected for uptake studies is of utmost importance. Counting the internalized colloids by number or by volume may lead to significantly different results. Third, colloids may change their physicochemical properties along their life cycle, and appropriate characterization is required during the different stages. [ABSTRACT FROM AUTHOR]

Abstract: Casein, a milk protein, is used to produce biotolerable and highly stable silver nanoparticles with a fair control over their size without using any additional reducing agent. These silver nanoparticles undergo reversible agglomeration to form protein–silver nanoparticle composite agglomerates as pH approaches to the isoelectric point of casein protein (pI =4.6). These agglomerates can then easily be re-dispersed in alkaline aqueous media with no obvious change in their optical properties. The nanoparticles can withstand high salt concentration (∼0.5M), and can also be freeze-dried, stored as dry powder and then dispersed in aqueous media whenever required. More interestingly, by controlling the concentration of casein protein and pH, it was also possible to control the self-assembly of silver nanoparticles to produce fairly uniform spherical agglomerates. The nanoparticles and their agglomerates were thoroughly characterized using UV–visible and FTIR spectroscopy, TEM, SEM and DLS, etc. Cytotoxicity of the hybrid materials was examined using a Resazurin based cytotoxicity assay. After determining the LD50 using NIH/3T3 fibroblast cells, the cellular interaction of these hybrid nanoparticles was studied to examine the behavior of casein-coated nanoparticles for their potential bio-applications. [Copyright &y& Elsevier]

Antibacterial agents are very important in the textile industry, water disinfection, medicine, and food packaging. Organic compounds used for disinfection have some disadvantages, including toxicity to the human body, therefore, the interest in inorganic disinfectants such as metal oxide nanoparticles (NPs) is increasing. This review focuses on the properties and applications of inorganic nanostructured materials and their surface modifications, with good antimicrobial activity. Such improved antibacterial agents locally destroy bacteria, without being toxic to the surrounding tissue. We also provide an overview of opportunities and risks of using NPs as antibacterial agents. In particular, we discuss the role of different NP materials. [ABSTRACT FROM AUTHOR]