15 Years of Small: Research Trends in Nanosafety.

In the field of nano- and microscale science and technology, Small has become one of the worldwide leading journals since its initiation 15 years ago. Among all the topics covered in Small, "nanosafety" has received growing interest over the years, which accounts for a large proportion of the total publications of Small. Herein, inspired by its coming Special Issue "Rethinking Nanosafety," a general bibliometric overview of the nanosafety studies that have been published in Small is presented. Using the data derived from the Web of Science Core Collection, the annual publication growth, most influential countries/institutions as well as the visualized collaborations between different countries and institutions based on CiteSpace software are presented. A special emphasis on the impact of the previous Special Issue from Small that is related to nanosafety research is given and the research trend from the most highly cited papers during last 15 years is analyzed. Lastly, future research directions are also proposed.

Making Conjugation-induced Fluorescent PEGylated Virus-like Particles by Dibromomaleimide-disulfide Chemistry.

The recent rise in virus-like particles (VLPs) in biomedical and materials research can be attributed to their ease of biosynthesis, discrete size, genetic programmability, and biodegradability. While they're highly amenable to bioconjugation reactions for adding synthetic ligands onto their surface, the range in bioconjugation methodologies on these aqueous born capsids is relatively limited. To facilitate the direction of functional biomaterials research, non-traditional bioconjugation reactions must be considered. The reaction described in this protocol uses dibromomaleimides to introduce new functionality in the solvent exposed disulfide bonds of a VLP based upon Bacteriophage Qß. Furthermore, the final product is fluorescent, which has the added benefit of generating a trackable in vitro probe using a commercially available filter set.

Characterizing workforces exposed to current and emerging non-carbonaceous nanomaterials in the U.S.

OBJECTIVE: Toxicology studies suggest that exposure to certain types of engineered nanomaterials (ENMs) may cause adverse health effects, but little is known about the workforce in the United States that produces or uses these materials. In addition, occupational exposure control strategies in this industry are not well characterized. This study identified U.S. ENM manufacturers and users (other than carbon nanotubes and nanofibers, which have been characterized elsewhere), determined workforce size, characterized types and quantities of materials used, occupational exposure control strategies, and the feasibility of occupational ENM exposure studies. METHODS: Eligible companies were identified and information was collected through phone surveys on nanomaterials produced or used, workforce size, location, work practices, and exposure control strategies. The companies were classified into groups for additional examinations. RESULTS: Forty-nine companies producing or using ENMs in the U.S. were identified. These companies employed at least 1,500 workers. Most companies produced or used some form of nanoscale metal. More than half of the eligible companies were suppliers for the coatings, composite materials, or general industries. Each company provided information about worker exposure reduction strategies through engineering controls, administrative controls, or personal protective equipment. Production-scale companies reported greater use of specific exposure control strategies for ENMs than laboratory-scale companies. CONCLUSIONS: Workplaces producing or using ENMs report using engineering and administrative controls as well as personal protective equipment to control worker exposure. Industrywide exposure assessment studies appear feasible due to workforce size. However, more effort must be taken to target industries using specific ENMs based on known toxicological effects and health risks.

Targeting tumor associated macrophages: The new challenge for nanomedicine.

The engineering of new nanomedicines with ability to target and kill or re-educate Tumor Associated Macrophages (TAMs) stands up as a promising strategy to induce the effective switching of the tumor-promoting immune suppressive microenvironment, characteristic of tumors rich in macrophages, to one that kills tumor cells, is anti-angiogenic and promotes adaptive immune responses. Alternatively, the loading of monocytes/macrophages in blood circulation with nanomedicines, may be used to profit from the high infiltration ability of myeloid cells and to allow the drug release in the bulk of the tumor. In addition, the development of TAM-targeted imaging nanostructures, can be used to study the macrophage content in solid tumors and, hence, for a better diagnosis and prognosis of cancer disease. The major challenges for the effective targeting of TAM with nanomedicines and their application in the clinic have already been identified. These challenges are associated to the undesirable clearance of nanomedicines by, the mononuclear phagocyte system (macrophages) in competing organs (liver, lung or spleen), upon their intravenous injection; and also to the difficult penetration of nanomedicines across solid tumors due to the abnormal vasculature and the excessive extracellular matrix present in stromal tumors. In this review we describe the recent nanotechnology-base strategies that have been developed to target macrophages in tumors.

Nanoliposomes carrying HER2/neu-derived peptide AE36 with CpG-ODN exhibit therapeutic and prophylactic activities in a mice TUBO model of breast cancer.

This study was designed to prepare and characterize nanoliposomal vaccine formulation encapsulating AE36 HER2/neu-derived peptide with or without CpG and evaluate the immunologic and therapeutic responses of that in BALB/c mice model of Her2 overexpressing breast cancer. AE36 was encapsulated in liposomes composed of DOTAP, DOPE and Cholesterol (DDC) or DD with. The formulations could induce both CD8+ and CD4+ responses and stimulate production of cytokines which was detected by Enzyme-linked immunospot assay (ELISpot) kits, cytotoxicity test and intracellular cytokine assay by flow cytometry. The formulation showed both therapeutic and prophylactic effects in BALB/c mice bearing Her2+ breast cancer. DDC+CpG showed the best effect in prophylactic study and DD+pG showed the best effect in therapeutic study, which both of them decreased the size of tumors significantly. The engineered nanoliposomes containing AE36 could be a candidate vaccine for the treatment or prophylaxis of HER2+ breast cancer and merits further investigation.

Assessment of Determinants of Emission Potentially Affecting the Concentration of Airborne Nano-Objects and Their Agglomerates and Aggregates.

Background: Nano-specific inhalation exposure models could potentially be effective tools to assess and control worker exposure to nano-objects, and their aggregates and agglomerates (NOAA). However, due to the lack of reliable and consistent collected NOAA exposure data, the scientific basis for validation of the existing NOAA exposure models is missing or limited. The main objective of this study was to gain more insight into the effect of various determinants underlying the potential on the concentration of airborne NOAA close to the source with the purpose of providing a scientific basis for existing and future exposure inhalation models. Method: Four experimental studies were conducted to investigate the effect of 11 determinants of emission on the concentration airborne NOAA close to the source during dumping of ~100% nanopowders. Determinants under study were: nanomaterial, particle size, dump mass, height, rate, ventilation rate, mixing speed, containment, particle surface coating, moisture content of the powder, and receiving surface. The experiments were conducted in an experimental room (19.5 m3) with well-controlled environmental and ventilation conditions. Particle number concentration and size distribution were measured using real-time measurement devices. Results: Dumping of nanopowders resulted in a higher number concentration and larger particles than dumping their reference microsized powder (P < 0.05). Statistically significant more and larger particles were also found during dumping of SiO2 nanopowder compared to TiO2/Al2O3 nanopowders. Particle surface coating did not affect the number concentration but on average larger particles were found during dumping of coated nanopowders. An increase of the powder's moisture content resulted in less and smaller particles in the air. Furthermore, the results indicate that particle number concentration increases with increasing dump height, rate, and mass and decreases when ventilation is turned on. Discussion: These results give an indication of the direction and magnitude of the effect of the studied determinants on concentrations close to the source and provide a scientific basis for (further) development of existing and future NOAA inhalation exposure models.

A new bifunctional hybrid nanostructure as an active platform for photothermal therapy and MR imaging.

As a bi-functional cancer treatment agent, a new hybrid nanostructure is presented which can be used for photothermal therapy by exposure to one order of magnitude lower laser powers compared to similar nanostructures in addition to substantial enhancment in magnetic resonance imaging (MRI) contrast. This gold-iron oxide hybrid nanostructure (GIHN) is synthesized by a cost-effective and high yield water-based approach. The GIHN is sheilded by PEG. Therefore, it shows high hemo and biocompatibility and more than six month stability. Alongside earlier nanostructures, the heat generation rate of GIHN is compareable with surfactnat-capped gold nanorods (GNRs). Two reasons are behind this enhancement: Firstly the distance between GNRs and SPIONs is adjusted in a way that the surface plasmon resonance of the new nanostructure is similar to bare GNRs and secondly the fraction of GNRs is raised in the hybrid nanostructure. GIHN is then applied as a photothermal agent using laser irradiation with power as low as 0.5 W.cm(-2) and only 32% of human breast adenocarcinoma cells could survive. The GIHN also acts as a dose-dependent transvers relaxation time (T2) MRI contrast agent. The results show that the GINH can be considered as a good candidate for multimodal photothermal therapy and MRI.

Surfactant-activated lipase hybrid nanoflowers with enhanced enzymatic performance.

Increasing numbers of materials have been extensively used as platforms for enzyme immobilization to improve catalytic performance. However, activity of the most of the enzymes was declined after immobilization. Here, we develop a surfactant-activated lipase-inorganic flowerlike hybrid nanomaterials with rational design based on interfacial activation and self-assembly. The resulting surfactant-activated lipase-inorganic hybird nanoflower (activated hNF-lipase) exhibited 460% and 200% higher activity than native lipase and conventional lipase-inorganic hybird nanoflower (hNF-lipase). Furthermore, the activated hNF-lipase displayed good reusability due to its monodispersity and mechanical properties, and had excellent long-time stability. The superior catalytic performances were attributed to both the conformational modulation of surfactants and hierarchical structure of nanoflowers, which not only anchored lipases in an active form, but also decreased the enzyme-support negative interaction and mass-transfer limitations. This new biocatalytic system is promising to find widespread use in applications related to biomedicine, biosensor, and biodiesel.

Development of nanostructures in the diagnosis of drug hypersensitivity reactions.

PURPOSE OF REVIEW: This article provides an overview of novel nanoscale structures potentially applicable to the field of allergy, and to discuss the required properties, advantages, and disadvantages of those nanostructures for clinical application focusing on diagnosis of drug hypersensitivity reactions. RECENT FINDINGS: Advances in the development of different nanostructures are favoring their biomedical applications. One area of interest is the interaction between nanostructures and the immune system, including their ability to emulate carrier molecules and their potential use for the diagnosis of allergic reactions. SUMMARY: Immunoassays are the most widely used in-vitro test for evaluating immunoglobulin E (IgE)-mediated drug hypersensitivity reactions. However, they have important technical limitations affecting their sensitivity. A wide variety of nanostructures have been designed to quantify specific IgE, with the aim of diagnosing different kinds of allergies. Nanoparticles-based colloidal immunoassay employed in microdevices and/or miniaturized systems are improving IgE detection sensitivity. Dendrimers have shown immense potential for the design and development of sensor platforms for evaluating IgE-mediated drug hypersensitivity reactions, due to the increase in hapten density and IgE accessibility. In this sense, a variety of dendritic structures as well as their hybridization to different solid supports have been shown to be successful when applied in the diagnosis of drug allergy. Moreover, the knowledge of the complete antigenic determinants would allow their inclusion and therefore further improvement of the sensitivity.

Recent Progress on Man-Made Inorganic Nanomachines.

The successful development of nanoscale machinery, which can operate with high controllability, high precision, long lifetimes, and tunable driving powers, is pivotal for the realization of future intelligent nanorobots, nanofactories, and advanced biomedical devices. However, the development of nanomachines remains one of the most difficult research areas, largely due to the grand challenges in fabrication of devices with complex components and actuation with desired efficiency, precision, lifetime, and/or environmental friendliness. In this work, the cutting-edge efforts toward fabricating and actuating various types of nanomachines and their applications are reviewed, with a special focus on nanomotors made from inorganic nanoscale building blocks, which are introduced according to the employed actuation mechanism. The unique characteristics and obstacles for each type of nanomachine are discussed, and perspectives and challenges of this exciting field are presented.

Nanomaterials in plant protection and fertilization: current state, foreseen applications, and research priorities.

Scientific publications and patents on nanomaterials (NM) used in plant protection or fertilizer products have exponentially increased since the millennium shift. While the United States and Germany have published the highest number of patents, Asian countries released most scientific articles. About 40% of all contributions deal with carbon-based NM, followed by titanium dioxide, silver, silica, and alumina. Nanomaterials come in many diverse forms (surprisingly often ≫100 nm), from solid doped particles to (often nonpersistent) polymer and oil-water based structures. Nanomaterials serve equally as additives (mostly for controlled release) and active constituents. Product efficiencies possibly increased by NM should be balanced against enhanced environmental NM input fluxes. The dynamic development in research and its considerable public perception are in contrast with the currently still very small number of NM-containing products on the market. Nanorisk assessment and legislation are largely in their infancies.

A road map toward a globally harmonized approach for occupational health surveillance and epidemiology in nanomaterial workers.

OBJECTIVE: Few epidemiological studies have addressed the health of workers exposed to novel manufactured nanomaterials. The small current workforce will necessitate pooling international cohorts. METHOD: A road map was defined for a globally harmonized framework for the careful choice of materials, exposure characterization, identification of study populations, definition of health endpoints, evaluation of appropriateness of study designs, data collection and analysis, and interpretation of the results. RESULTS: We propose a road map to reach global consensus on these issues. The proposed strategy should ensure that the costs of action are not disproportionate to the potential benefits and that the approach is pragmatic and practical. CONCLUSIONS: We should aim to go beyond the collection of health complaints, illness statistics, or even counts of deaths; the manifestation of such clear endpoints would indicate a failure of preventive measures.

Estimating production data for five engineered nanomaterials as a basis for exposure assessment.

The magnitude of engineered nanomaterials (ENMs) being produced and potentially released to the environment is a crucial and thus far unknown input to exposure assessment. This work estimates upper and lower bound annual United States production quantities for 5 classes of ENMs. A variety of sources were culled to identify companies producing source ENM products and determine production volumes. Using refining assumptions to attribute production levels from companies with more reliable estimates to companies with little to no data, ranges of U.S. production quantities were projected for each of the 5 ENMs. The quality of data is also analyzed; the percentage of companies for which data were available (via Web sites, patents, or direct communication) or unavailable (and thus extrapolated from other companies' data) is presented.

Toxicology of engineered nanomaterials: focus on biocompatibility, biodistribution and biodegradation.

BACKGROUND: It is widely believed that engineered nanomaterials will be increasingly used in biomedical applications. However, before these novel materials can be safely applied in a clinical setting, their biocompatibility, biodistribution and biodegradation needs to be carefully assessed. SCOPE OF REVIEW: There are a number of different classes of nanoparticles that hold promise for biomedical purposes. Here, we will focus on some of the most commonly studied nanomaterials: iron oxide nanoparticles, dendrimers, mesoporous silica particles, gold nanoparticles, and carbon nanotubes. MAJOR CONCLUSIONS: The mechanism of cellular uptake of nanoparticles and the biodistribution depend on the physico-chemical properties of the particles and in particular on their surface characteristics. Moreover, as particles are mainly recognized and engulfed by immune cells special attention should be paid to nano-immuno interactions. It is also important to use primary cells for testing of the biocompatibility of nanoparticles, as they are closer to the in vivo situation when compared to transformed cell lines. GENERAL SIGNIFICANCE: Understanding the unique characteristics of engineered nanomaterials and their interactions with biological systems is key to the safe implementation of these materials in novel biomedical diagnostics and therapeutics. This article is part of a Special Issue entitled Nanotechnologies - Emerging Applications in Biomedicine.

Properties and applications of colloidal nonspherical noble metal nanoparticles.

Nanoparticles of noble metals belong to the most extensively studied colloidal systems in the field of nanoscience and nanotechnology. Due to continuing progress in the synthesis of nanoparticles with controlled morphologies, the exploration of unique morphology-dependent properties has gained momentum. Anisotropic features in nonspherical nanoparticles make them ideal candidates for enhanced chemical, catalytic, and local field related applications. Nonspherical plasmon resonant nanoparticles offer favorable properties for their use as analytical tools, or as diagnostic and therapeutic agents. This Review highlights morphology-dependent properties of nonspherical noble metal nanoparticles with a focus on localized surface plasmon resonance and local field enhancement, as well as their applications in various fields including Raman spectroscopy, fluorescence enhancement, analytics and sensing, photothermal therapy, (bio-)diagnostics, and imaging.

[Provision of the population with sanitary-and-epidemiological wellbeing under conditions of extended use of nanomaterials and nanotechnologies].

As of now, work is ever increasingly and successfully proceeding on the development of nanotechnologies and promising nanomaterials. By 2015, the nanotechnology product market may be expected to amount to US$ 1.2-2.9 trillion. Nanotechnology as a set of methods for the controlled manipulation of material objects with the sizes of less than 100 nm makes it possible to use a substance with a traditional chemical composition to design structures in the nanometer range (nanomaterials) and to endow them with fundamentally new properties, such as unique mechanical strength, special spectral, electrical, magnetic, chemical, and biological characteristics. Among the main domains for applications of nanomaterials, we should now single out optics, power engineering, researches, wildlife conservation, etc. The specific physicochemical properties of nanomaterials suggest that they can be toxic to humans. That is the reason that society should be keenly aware of what the nanomaterials are. Despite the fact that nanomaterials have been already used worldwide for more than 10 years, none kind has been fully investigated for its safety in any country.