Characterization of nanomaterial dispersion in solution prior to in vitro exposure using dynamic light scattering technique.

The need to characterize nanoparticles in solution before assessing the in vitro toxicity is a high priority. Particle size, size distribution, particle morphology, particle composition, surface area, surface chemistry, and particle reactivity in solution are important factors which need to be defined to accurately assess nanoparticle toxicity. Currently, there are no well-defined techniques for characterization of wet nanomaterials in aqueous or biological solutions. Previously reported nanoparticle characterization techniques in aqueous or biological solutions have consisted of the use of ultra-high illumination light microscopy and disc centrifuge sedimentation; however, these techniques are limited by the measurement size range. The current study focuses on characterizing a wide range of nanomaterials using dynamic light scattering (DLS) and transmission electron microscopy, including metals, metal oxides, and carbon-based materials, in water and cell culture media, with and without serum. Cell viability and cell morphology studies were conducted in conjunction with DLS experiments to evaluate toxicological effects from observed agglomeration changes in the presence or absence of serum in cell culture media. Observations of material-specific surface properties were also recorded. It was also necessary to characterize the impact of sonication, which is implemented to aid in particle dispersion and solution mixture. Additionally, a stock solution of nanomaterials used for toxicology studies was analyzed for changes in agglomeration and zeta potential of the material over time. In summary, our results demonstrate that many metal and metal oxide nanomaterials agglomerate in solution and that depending upon the solution particle agglomeration is either agitated or mitigated. Corresponding toxicity data revealed that the addition of serum to cell culture media can, in some cases, have a significant effect on particle toxicity possibly due to changes in agglomeration or surface chemistry. It was also observed that sonication slightly reduces agglomeration and has minimal effect on particle surface charge. Finally, the stock solution experienced significant changes in particle agglomeration and surface charge over time.     

Analysis of titanium dioxide and zinc oxide nanoparticles in cosmetics

There have been rapid increases in consumer products containing nanomaterials, raising concerns over the impact of nanoparticles (NPs) to humankind and the environment, but little information has been published about mineral filters in commercial sunscreens. It is urgent to develop methods to characterize the nanomaterials in products. Titanium dioxide (TiO₂) and zinc oxide (ZnO) NPs in unmodified commercial sunscreens were characterized by laser scanning confocal microscopy, atomic force microscopy, X-ray diffraction (XRD), and transmission electron microscopy (TEM). The results showed that laser scanning confocal microscopy evaluated primary particle aggregates and dispersions but could not size NPs because of the diffraction limited resolution of optical microscopy (200 nm). Atomic force microscopy measurements required a pretreatment of the sunscreens or further calibration in phase analysis, but could not provide their elemental composition of commercial sunscreens. While XRD gave particle size and crystal information without a pretreatment of sunscreen, TEM analysis required dilution and dispersion of the commercial sunscreens before imaging. When coupled with energy-dispersive X-ray spectroscopy, TEM afforded particle size information and compositional analysis. XRD characterization of six commercial sunscreens labeled as nanoparticles revealed that three samples contained TiO₂ NPs, among which two listed ZnO and TiO₂, and displayed average particle sizes of 15 nm, 21 nm, and 78 nm. However, no nanosized ZnO particles were found in any of the samples by XRD. In general, TEM can resolve nanomaterials that exhibit one or more dimensions between 1 nm and 100 nm, allowing the identification of ZnO and TiO₂ NPs in all six sunscreens and ZnO/TiO₂ mixtures in two of the samples. Overall, the combination of XRD and TEM was suitable for analyzing ZnO and TiO₂ NPs in commercial sunscreens.     

Comparison of scanning electron microscopy, dynamic light scattering and analytical ultracentrifugation for the sizing of poly(butyl cyanoacrylate) nanoparticles.

Nanoparticles represent promising carriers for controlled drug delivery. This work focuses on the size and molecular mass characterization of polyalkylcyanoacrylate nanoparticles formed by anionic emulsion polymerization of butylcyanoacrylate in the presence of poloxamer 188 as a stabilizer. Three different methods were used to determine the size and size distribution of the particle populations: scanning electron microscopy (SEM), dynamic light scattering (DLS), and analytical ultracentrifugation (ANUC). SEM on freeze-dried and Au-shadowed samples showed a relatively narrow distribution of virtually spherical particles with a mean diameter of 167 nm. DLS yielded a monomodal distribution with hydrodynamic diameters around 199 nm (in the absence of additional stabilizer) or 184 nm (in the presence of 1% poloxamer 188). The size distribution determined by ANUC using sedimentation velocity analysis was somewhat more complex, the size of the most abundant particles being around 184 nm. Molar particle mass distributions centered around 2.3x10(9) g/mol. The advantages and disadvantages of the three sizing techniques are discussed.     

Research in bioanalysis and separations at the University of Nebraska - Lincoln

The Chemistry Department at the University of Nebraska - Lincoln (UNL) is located in Hamilton Hall on the main campus of UNL in Lincoln, NE, USA. This department houses the primary graduate and research program in chemistry in the state of Nebraska. This program includes the traditional fields of analytical chemistry, biochemistry, inorganic chemistry, organic chemistry and physical chemistry. However, this program also contains a great deal of multidisciplinary research in fields that range from bioanalytical and biophysical chemistry to nanomaterials, energy research, catalysis and computational chemistry. Current research in bioanalytical and biophysical chemistry at UNL includes work with separation methods such as HPLC and CE, as well as with techniques such as MS and LC-MS, NMR spectroscopy, electrochemical biosensors, scanning probe microscopy and laser spectroscopy. This article will discuss several of these areas, with an emphasis being placed on research in bioanalytical separations, binding assays and related fields.     

Testing Strategies to Establish the Safety of Nanomaterials: Conclusions of an ECETOC Workshop

The European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) convened a workshop in Barcelona, Spain, in November 2005 to develop testing strategies to establish the safety of nanomaterials. It brought together about 70 scientific and clinical experts from industry, academia, government agencies, research institutes, and nongovernmental organizations. The primary questions to be addressed were the following: What can we do today, and what do we need tomorrow? The three major themes of the workshop were: (1) the need for enhanced efforts in nanomaterial characterization; (2) methodologies for assessments of airborne and internal exposures to nanomaterials; and (3) evaluation of the hazard potential—primarily focusing on pulmonary or dermal routes of exposures. Some of the summary conclusions of the workshop included the following: For the development of nanoparticle characterization, the working definition of nanoparticles was defined as < 100 nm in one dimension or < 1000 nm to include aggregates and agglomerates. Moreover, it was concluded that although many physical factors can influence toxicity, including nanoparticle composition, it is dissolution, surface area and characteristics, size, size distribution, and shape that largely determine the functional, toxicological and environmental impact of nanomaterials. In addition, most of the information on potential systemic effects has thus far been derived from combustion-generated particles. With respect to the assessment of external exposures and metrics appropriate for nanoparticles, the general view of the meeting was that currently it is not possible or desirable to select one form of dose metric (i.e., mass, surface area, or particle number) as the most appropriate measure source. However, it was clear that the surface area metric was likely to be of interest and requires further development. In addition, there is a clear and immediate need to develop instruments which are smaller, more portable, and less expensive than the currently available state of the art instrumentation. With regard to a general testing approach for human health hazard evaluation of nanoparticles, a first step to determine potency may include a prioritization-related in vitro screening strategy to assess the possible reactivity, biomarkers of inflammation and cellular uptake of nanoparticles; however this process should be validated using in vivo techniques. A Tier 1 in vivo testing strategy could include a short-term inhalation or intratracheal instillation of nanoparticles as the route of exposure in the lungs of rats or mice. The endpoints that should be assessed include indices of lung inflammation, cytotoxicity, and cell proliferation, as well as histopathology of the respiratory tract and the major extrapulmonary organs. For Tier 2 in vivo testing for hazard identification, a longer term inhalation study is recommended, and this would include more substantive mechanistic endpoints such as determination of particle deposition, translocation, and disposition within the body. Additional studies could be designed with specific animal models to mimic sensitive populations. With regard to dermal exposures, currently there is little evidence that nanoparticles at a size exceeding 100 nm penetrate through the skin barrier into the living tissue (i.e., dermal compartment). The penetration of nanoparticles at a size less than 100 nm should be a topic of further investigation. Moreover, considering the impacts of dermal exposures and corresponding hazard potential of nanoparticles, it must be taken into consideration that the dermal uptake of nanoparticles will be an order of magnitude smaller than the uptake via the inhalation or oral routes of exposure. For the evaluation of the health risk of nanoparticles, it has to be determined whether they are harmful to living cells and whether, under real conditions, they penetrate through the skin barrier into the living tissue. For the evaluation of the penetration processes, in principle, three methods are available. Using the method of differential stripping, the penetration kinetics of nanoparticles in the stratum corneum and the hair follicles can be evaluated. This analysis can be carried out in vivo. Diffusion cell experiments are an efficient method for in vitro penetration studies. Also, laser scanning microscopy is well suited to test penetration kinetics, although requiring fluorescent-labeled nanoparticles. Emerging topics such as (1) environmental safety testing, (2) applications of nanoparticles for medical purposes, and (3) pathways of inhaled nanoparticles to the central nervous system were also briefly addressed during this workshop. However, it has become clear that these topics should be the subjects of separate workshops and they are not further addressed in this report.     

Development of a PIXE analysis method for the determination of the biopersistence of SiC and TiC nanoparticles in rat lungs

With the advent of nanoparticles produced in high quantities and employed in products or processes, the need to evaluate their potential toxicological effects is necessary. For this purpose, biopersistence studies are needed to assess the possible effects of nanoparticles in parallel with a proper characterization. The insoluble character of many nanomaterials makes traditional chemical analytical methods unapplicable for the ex-vivo measurements of their concentration in organs. Ion beam-based techniques such as Particle-Induced X-ray Emission (PIXE) can solve this difficulty. We illustrate that by the measurement of biopersistence of SiC and TiC nanoparticles instilled in rats lungs and investigated over a 60-day time span. The results can be obtained within minutes and the limits of detection are within ppm levels.     

Testing strategies to establish the safety of nanomaterials: conclusions of an ECETOC workshop

The European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) convened a workshop in Barcelona, Spain, in November 2005 to develop testing strategies to establish the safety of nanomaterials. It brought together about 70 scientific and clinical experts from industry, academia, government agencies, research institutes, and nongovernmental organizations. The primary questions to be addressed were the following: What can we do today, and what do we need tomorrow? The three major themes of the workshop were: (1) the need for enhanced efforts in nanomaterial characterization; (2) methodologies for assessments of airborne and internal exposures to nanomaterials; and (3) evaluation of the hazard potential--primarily focusing on pulmonary or dermal routes of exposures. Some of the summary conclusions of the workshop included the following: For the development of nanoparticle characterization, the working definition of nanoparticles was defined as < 100 nm in one dimension or < 1000 nm to include aggregates and agglomerates. Moreover, it was concluded that although many physical factors can influence toxicity, including nanoparticle composition, it is dissolution, surface area and characteristics, size, size distribution, and shape that largely determine the functional, toxicological and environmental impact of nanomaterials. In addition, most of the information on potential systemic effects has thus far been derived from combustion-generated particles. With respect to the assessment of external exposures and metrics appropriate for nanoparticles, the general view of the meeting was that currently it is not possible or desirable to select one form of dose metric (i.e., mass, surface area, or particle number) as the most appropriate measure source. However, it was clear that the surface area metric was likely to be of interest and requires further development. In addition, there is a clear and immediate need to develop instruments which are smaller, more portable, and less expensive than the currently available state of the art instrumentation. With regard to a general testing approach for human health hazard evaluation of nanoparticles, a first step to determine potency may include a prioritization-related in vitro screening strategy to assess the possible reactivity, biomarkers of inflammation and cellular uptake of nanoparticles; however this process should be validated using in vivo techniques. A Tier 1 in vivo testing strategy could include a short-term inhalation or intratracheal instillation of nanoparticles as the route of exposure in the lungs of rats or mice. The endpoints that should be assessed include indices of lung inflammation, cytotoxicity, and cell proliferation, as well as histopathology of the respiratory tract and the major extrapulmonary organs. For Tier 2 in vivo testing for hazard identification, a longer term inhalation study is recommended, and this would include more substantive mechanistic endpoints such as determination of particle deposition, translocation, and disposition within the body. Additional studies could be designed with specific animal models to mimic sensitive populations. With regard to dermal exposures, currently there is little evidence that nanoparticles at a size exceeding 100 nm penetrate through the skin barrier into the living tissue (i.e., dermal compartment). The penetration of nanoparticles at a size less than 100 nm should be a topic of further investigation. Moreover, considering the impacts of dermal exposures and corresponding hazard potential of nanoparticles, it must be taken into consideration that the dermal uptake of nanoparticles will be an order of magnitude smaller than the uptake via the inhalation or oral routes of exposure. For the evaluation of the health risk of nanoparticles, it has to be determined whether they are harmful to living cells and whether, under real conditions, they penetrate through the skin barrier into the living tissue. For the evaluation of the penetration processes, in principle, three methods are available. Using the method of differential stripping, the penetration kinetics of nanoparticles in the stratum corneum and the hair follicles can be evaluated. This analysis can be carried out in vivo. Diffusion cell experiments are an efficient method for in vitro penetration studies. Also, laser scanning microscopy is well suited to test penetration kinetics, although requiring fluorescent-labeled nanoparticles. Emerging topics such as (1) environmental safety testing, (2) applications of nanoparticles for medical purposes, and (3) pathways of inhaled nanoparticles to the central nervous system were also briefly addressed during this workshop. However, it has become clear that these topics should be the subjects of separate workshops and they are not further addressed in this report.     

Application of different analytical methods for the characterization of non-spherical micro- and nanoparticles

Non-spherical micro- and nanoparticles have recently gained considerable attention due to their surprisingly different interaction with biological systems compared to their spherical counterparts, opening new opportunities for drug delivery and vaccination. Up till now, electron microscopy is the only method to quantitatively identify the critical quality attributes (CQAs) of non-spherical particles produced by film-stretching; namely size, morphology and the quality of non-spherical particles (degree of contamination with spherical ones). However, electron microscopy requires expensive instrumentation, demanding sample preparation and non-trivial image analysis. To circumvent these drawbacks, the ability of different particle analysis methods to quantitatively identify the CQA of spherical and non-spherical poly(1-phenylethene-1,2-diyl (polystyrene) particles over a wide size range (40 nm, 2 μm and 10 μm) was investigated. To this end, light obscuration, image-based analysis methods (Microflow imaging, MFI, and Vi-Cell XR Coulter Counter) and flow cytometry were used to study particles in the micron range, while asymmetric flow field fractionation (AF4) coupled to multi-angle laser scattering (MALS) and quasi elastic light scattering (QELS) was used for particles in the nanometer range, and all measurements were benchmarked against electron microscopy. Results show that MFI can reliably identify particle size and aspect ratios of the 10 μm particles, but not the 2 μm ones. Meanwhile, flow cytometry was able to differentiate between spherical and non-spherical 10 or 2 μm particles, and determine the amount of impurities in the sample. As for the nanoparticles, AF4 coupled to MALS and QELS allowed the measurement of the geometric (r_g) and hydrodynamic (r_h) radii of the particles, as well as their shape factors (r_g/r_h), confirming their morphology. While this study shows the utility of MFI, flow cytometry and AF4 for quantitative evaluation of the CQA of non-spherical particles over a wide size range, the limitations of the methods are discussed. The use of orthogonal characterization methods can provide a complete picture about the CQA of non-spherical particles over a wide size range.     

PLGA nanoparticles in drug delivery: the state of the art

Nanoparticles represent drug delivery systems suitable for most administration routes. Over the years, a variety of natural and synthetic polymers have been explored for the preparation of nanoparticles, of which Poly(lactic acid) (PLA), Poly(glycolic acid) (PGA), and their copolymers (PLGA) have been extensively investigated because of their biocompatibility and biodegradability. Nanoparticles act as potential carries for several classes of drugs such as anticancer agents, antihypertensive agents, immunomodulators, and hormones; and macromolecules such as nucleic acids, proteins, peptides, and antibodies. The options available for preparation have increased with advances in traditional methods, and many novel techniques for preparation of drug-loaded nanoparticles are being developed and refined. The various methods used for preparation of nanoparticles with their advantages and limitations have been discussed. The crux of the problem is the stability of nanoparticles after preparation, which is being addressed by freeze-drying using different classes of lyoprotectants. Nanoparticles can be designed for the site-specific delivery of drugs. The targeting capability of nanoparticles is influenced by particle size, surface charge, surface modification, and hydrophobicity. Finally, the performance of nanoparticles in vivo is influenced by morphological characteristics, surface chemistry, and molecular weight. Careful design of these delivery systems with respect to target and route of administration may solve some of the problems faced by new classes of active molecules.     

Non-invasive determination of cellular oxygen consumption as novel cytotoxicity assay for nanomaterials

Investigating the safety of nanoparticles is essential for many fields of their applications, in particular for consumer products, food and medicines. The conventional dye and fluorescence-based cytotoxicity assays are limited by the interference of such readouts with nanomaterials. This holds in particular when nanomaterials have been fluorescently labelled for other purposes, for example, confocal microscopy. Moreover, most of these assays are invasive, that is, typically involve irreversible changes or destruction of cells and hence only allowing one endpoint measurement. Therefore, a non-invasive method for the detection of cytotoxicity was developed which is based on the automated online monitoring of the oxygen concentration in solution (SensorDish® Reader). Fluorescently labelled silica nanoparticles with different sizes and surface modifications were used as model systems to explore this novel assay. Thereby, the SensorDish® Reader allows a life documentation of the cellular behaviour and clarifies that size, time, concentration and surface modification of nanoparticles affect cellular viability.     

Colloidal behaviors of ZnO nanoparticles in various aqueous media

We have evaluated the particle sizes, zeta potentials and hydrodynamic radii of zinc oxide (ZnO) nanoparticles in various aqueous conditions such as deionized water, phosphate buffered saline and Minimum Essential Media Eagle. In order to study the size and surface chemistry effect in colloidal behaviors, different size of 20 and 70 nm ZnO nanoparticles were selected and their surface was modified with either citrate or L-serine. It was revealed that surface modification did not strongly affect the particle size or morphology but altered the surface charge and chemistry. In various aqueous media, although the surface charge of ZnO nanoparticles are slightly affected by the existence of electrolyte, the overall particle sizes and morphologies are determined to be preserved, suggesting that their properties as nanoparticles are not significantly changed in physiological conditions.     

Research Spotlight: The next big thing is actually small

Recent developments in materials, surface modifications, separation schemes, detection systems and associated instrumentation have allowed significant advances in the performance of lab-on-a-chip devices. These devices, also referred to as micro total analysis systems (μTAS), offer great versatility, high throughput, short analysis time, low cost and, more importantly, performance that is comparable to standard bench-top instrumentation. To date, μTAS have demonstrated advantages in a significant number of fields including biochemical, pharmaceutical, military and environmental. Perhaps most importantly, μTAS represent excellent platforms to introduce students to microfabrication and nanotechnology, bridging chemistry with other fields, such as engineering and biology, enabling the integration of various skills and curricular concepts. Considering the advantages of the technology and the potential impact to society, our research program aims to address the need for simpler, more affordable, faster and portable devices to measure biologically active compounds. Specifically, the program is focused on the development and characterization of a series of novel strategies towards the realization of integrated microanalytical devices. One key aspect of our research projects is that the developed analytical strategies must be compatible with each other; therefore, enabling their use in integrated devices. The program combines spectroscopy, surface chemistry, capillary electrophoresis, electrochemical detection and nanomaterials. This article discusses some of the most recent results obtained in two main areas of emphasis: capillary electrophoresis, microchip-capillary electrophoresis, electrochemical detection and interaction of proteins with nanomaterials.     

Approach to using mechanism-based structure activity relationship (SAR) analysis to assess human health hazard potential of nanomaterials

With the increasing use and development of engineered nanoparticles in electronics, consumer products, pesticides, food and pharmaceutical industries, there is a growing concern about potential human health hazards of these materials. A number of studies have demonstrated that nanoparticle toxicity is extremely complex, and that the biological activity of nanoparticles will depend on a variety of physicochemical properties such as particle size, shape, agglomeration state, crystal structure, chemical composition, surface area and surface properties. Nanoparticle toxicity can be attributed to nonspecific interaction with biological structures due to their physical properties (e.g., size and shape) and biopersistence, or to specific interaction with biomolecules through their surface properties (e.g., surface chemistry and reactivity) or release of toxic ions. The toxic effects of most nanomaterials have not been adequately characterized and currently, there are many issues and challenges in toxicity testing and risk assessment of nanoparticles. Based on the possible mechanisms of action and available in vitro and in vivo toxicity database, this paper proposes an approach to using mechanism-based SAR analysis to assess the relative human health hazard/risk potential of various types of nanomaterials.     

Intracellular accumulation and dissolution of silver nanoparticles in L-929 fibroblast cells using live cell time-lapse microscopy

Cytotoxicity assessments of nanomaterials, such as silver nanoparticles, are challenging due to interferences with test reagents and indicators as well uncertainties in dosing as a result of the complex nature of nanoparticle intracellular accumulation. Furthermore, current theories suggest that silver nanoparticle cytotoxicity is a result of silver nanoparticle dissolution and subsequent ion release. This study introduces a novel technique, nanoparticle associated cytotoxicity microscopy analysis (NACMA), which combines fluorescence microscopy detection using ethidium homodimer-1, a cell permeability marker that binds to DNA after a cell membrane is compromised (a classical dead-cell indicator dye), with live cell time-lapse microscopy and image analysis to simultaneously investigate silver nanoparticle accumulation and cytotoxicity in L-929 fibroblast cells. Results of this method are consistent with traditional methods of assessing cytotoxicity and nanoparticle accumulation. Studies conducted on 10, 50, 100 and 200?nm silver nanoparticles reveal size dependent cytotoxicity with particularly high cytotoxicity from 10?nm particles. In addition, NACMA results, when combined with transmission electron microscopy imaging, reveal direct evidence of intracellular silver ion dissolution and possible nanoparticle reformation within cells for all silver nanoparticle sizes.     

Current in vitro methods in nanoparticle risk assessment: Limitations and challenges

Nanoparticles are an emerging class of functional materials defined by size-dependent properties. Application fields range from medical imaging, new drug delivery technologies to various industrial products. Due to the expanding use of nanoparticles, the risk of human exposure rapidly increases and reliable toxicity test systems are urgently needed. Currently, nanoparticle cytotoxicity testing is based on in vitro methods established for hazard characterization of chemicals. However, evidence is accumulating that nanoparticles differ largely from these materials and may interfere with commonly used test systems. Here, we present an overview of current in vitro toxicity test methods for nanoparticle risk assessment and focus on their limitations resulting from specific nanoparticle properties. Nanoparticle features such as high adsorption capacity, hydrophobicity, surface charge, optical and magnetic properties, or catalytic activity may interfere with assay components or detection systems, which has to be considered in nanoparticle toxicity studies by characterization of specific particle properties and a careful test system validation. Future studies require well-characterized materials, the use of available reference materials and an extensive characterization of the applicability of the test methods employed. The resulting challenge for nanoparticle toxicity testing is the development of new standardized in vitro methods that cannot be affected by nanoparticle properties.     

The ecotoxicology and chemistry of manufactured nanoparticles

The emerging literature on the ecotoxicity of nanoparticles and nanomaterials is summarised, then the fundamental physico-chemistry that governs particle behaviour is explained in an ecotoxicological context. Techniques for measuring nanoparticles in various biological and chemical matrices are also outlined. The emerging ecotoxicological literature shows toxic effects on fish and invertebrates, often at low mg l⁻¹ concentrations of nanoparticles. However, data on bacteria, plants, and terrestrial species are particularly lacking at present. Initial data suggest that at least some manufactured nanoparticles may interact with other contaminants, influencing their ecotoxicity. Particle behaviour is influenced by particle size, shape, surface charge, and the presence of other materials in the environment. Nanoparticles tend to aggregate in hard water and seawater, and are greatly influenced by the specific type of organic matter or other natural particles (colloids) present in freshwater. The state of dispersion will alter ecotoxicity, but many abiotic factors that influence this, such as pH, salinity, and the presence of organic matter remain to be systematically investigated as part of ecotoxicological studies. Concentrations of manufactured nanoparticles have rarely been measured in the environment to date. Various techniques are available to characterise nanoparticles for exposure and dosimetry, although each of these methods has advantages and disadvantages for the ecotoxicologist. We conclude with a consideration of implications for environmental risk assessment of manufactured nanoparticles.     

In vitro cytotoxicity of nanoparticles in mammalian germline stem cells.

Gametogenesis is a complex biological process that is particularly sensitive to environmental insults such as chemicals. Many chemicals have a negative impact on the germline, either by directly affecting the germ cells, or indirectly through their action on the somatic nursing cells. Ultimately, these effects can inhibit fertility, and they may have negative consequences for the development of the offspring. Recently, nanomaterials such as nanotubes, nanowires, fullerene derivatives (buckyballs), and quantum dots have received enormous national attention in the creation of new types of analytical tools for biotechnology and the life sciences. Despite the wide application of nanomaterials, there is a serious lack of information concerning their impact on human health and the environment. Thus, there are limited studies available on toxicity of nanoparticles for risk assessment of nanomaterials. The purpose of this study was to assess the suitability of a mouse spermatogonial stem cell line as a model to assess nanotoxicity in the male germline in vitro. The effects of different types of nanoparticles on these cells were evaluated by light microscopy, and by cell proliferation and standard cytotoxicity assays. Our results demonstrate a concentration-dependent toxicity for all types of particles tested, whereas the corresponding soluble salts had no significant effect. Silver nanoparticles were the most toxic while molybdenum trioxide (MoO(3)) nanoparticles were the least toxic. Our results suggest that this cell line provides a valuable model with which to assess the cytotoxicity of nanoparticles in the germ line in vitro.     

Characterization of lipid nanoparticles by differential scanning calorimetry, X-ray and neutron scattering

Differential scanning calorimetry and X-ray diffraction play a prominent role in the characterization of lipid nanoparticle (LNP) dispersions. This review shortly outlines the measurement principles of these two techniques and summarizes their applications in the field of nanodispersions of solid lipids. These methods are particularly useful for the characterization of the matrix state, polymorphism and phase behavior of the nanoparticles which may be affected by, for example, the small particle size and the composition of the dispersions. The basics of small angle X-ray and neutron scattering which are also very promising methods for the characterization of LNPs are explained in some more detail. Examples for their use in the area of solid LNPs regarding the evaluation of particle size effects and the formation of superstructures in the nanoparticle dispersions are given. Some technical questions concerning the use of the different characterization techniques in the field of LNP research are also addressed.     

纳米材料诱导肺部疾病及其机制研究进展

随着纳米科技的飞速发展, 纳米材料凭借其独特的理化性能在材料、 工业、 环保、 军事、 医药等多个领域扮 演着重要的角色。纳米材料的生产和使用, 使其不可避免地进入生态系统, 人们可通过环境暴露、 职业暴露和医源 性暴露接触到纳米材料。呼吸系统是纳米材料进入人体的最主要途径。大量研究证实, 吸入的纳米材料主要通过 氧化应激、 炎症反应和离子紊乱等毒性机制对肺造成损伤, 诱导肉芽肿病变、 肺纤维化、 哮喘、 慢性阻塞性肺疾病, 甚 至肺癌等肺部疾病的发生。本文对纳米材料暴露与肺部疾病的关系及其肺毒性作用机制进行简要综述。     

Biopharmaceutics and therapeutic potential of engineered nanomaterials

Engineered nanomaterials are at the leading edge of the rapidly developing nanosciences and are founding an important class of new materials with specific physicochemical properties different from bulk materials with the same compositions. The potential for nanomaterials is rapidly expanding with novel applications constantly being explored in different areas. The unique size-dependent properties of nanomaterials make them very attractive for pharmaceutical applications. Investigations of physical, chemical and biological properties of engineered nanomaterials have yielded valuable information. Cytotoxic effects of certain engineered nanomaterials towards malignant cells form the basis for one aspect of nanomedicine. It is inferred that size, three dimensional shape, hydrophobicity and electronic configurations make them an appealing subject in medicinal chemistry. Their unique structure coupled with immense scope for derivatization forms a base for exciting developments in therapeutics. This review article addresses the fate of absorption, distribution, metabolism and excretion (ADME) of engineered nanoparticles in vitro and in vivo. It updates the distinctive methodology used for studying the biopharmaceutics of nanoparticles. This review addresses the future potential and safety concerns and genotoxicity of nanoparticle formulations in general. It particularly emphasizes the effects of nanoparticles on metabolic enzymes as well as the parenteral or inhalation administration routes of nanoparticle formulations. This paper illustrates the potential of nanomedicine by discussing biopharmaceutics of fullerene derivatives and their suitability for diagnostic and therapeutic purposes. Future direction is discussed as well.