Chapter
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Nanotechnology has a global socioeconomic significance. On the brighter side, Nanoparticles (NPs) offer extraordinary technical competencies which allow them to perform enormously novel developments in science and industries. Whereas, on the darker side, just the same novel qualities of nanoparticles can concurrently evoke undesired features, which sometimes lead to adverse and harmful interactions with exposed organisms. Workers involved in manufacturing and handling of NPs in all countries face new hazards from these nanomaterials. The occupational safety and health associations have taken schemes to spot the gaps between awareness and practices. These international agencies formulate the guidelines for handling nano materials and fix their occupational exposure limits. In this chapter authors discussed the source and role of NPs in different areas, NPs induced toxicity, their interaction with different biomolecules, as well as the safety and handling guidelines of NPs in occupational and laboratory areas.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

Article
The desire for humanity and the desire for security have co-existed as long as humans have been alive. As science has become increasingly sophisticated, so have the methods of self-defence by States. Nanotechnology is already changing warfare by increasing capabilities upon which armed forces are heavily reliant: more efficient energy storage, advanced photovoltaics, and improved military protective equipment, to name a few of these developments. Some applications of nanomaterials by the military are both powerful and subtle, and have neurological and biological applications. The advance of the use or contemplation of use of these types of nanoscale applications by the military requires urgent analysis in light of existing international law, particularly in light of their potential effects on humans and on the environment.
Chapter
This chapter explores nanomaterials (NMs) and nanoparticles (NPs) with a focus on their detrimental effects in society and in our daily life. NPs have the ability to enter the body and damage the living organisms in the body. NPs are small in size and may enter in the human body through the lungs or by penetrating the skin barriers, enter the body’s circulatory system, and travel throughout the body, potentially disturbing the whole system. In general, NPs have a toxic manifestation and will cause and create allergies. They may also lead to fibrosis, organ failure, nephrotoxicity, hematological toxicities, neurotoxicity, herpetological toxicities, and so on. The number of commercial products containing NMs is growing and are found in the personal care, cosmetics, and sunscreen categories. Other products include NMs such as electronic equipment, textiles, and composite plastics. They are disposed of by recycling, energy recovery, waste incineration, or landfilling, as defined in the hierarchy of disposal options. Recycling operations are not always helpful when it comes to NMs, as they are carried out by using the techniques that meet the general standards of an environmentally sound waste management process for products that do not contain NMs. These operations may not be enough to manage waste NPs in a safe and environmentally sound manner, which may give rise to other problems.
Chapter
The surge in nanobiotechnology has given rise to successful utilization of nanoparticles in several novel applications in agriculture, industry, and the biomedical field. However, nanoparticles have a more pronounced effect in systems with respect to inflammation and cell damage as compared to an equal mass of particles having greater size. They are known to induce pulmonary, cutaneous, cardiovascular, and xenotoxicity. The engineered nanoparticles, owing to their high reactivity, have the capacity to initiate inflammatory responses that act as a trigger for metastasis. Huge knowledge gaps exist with respect to the nature of nanoparticles and their interaction with different environmental components. Apart from beneficial reports, there have been numerous studies implicating nanoparticles in plant toxicity through chromosomal abnormalities, oxidative damages to biological membranes, decreased photosynthetic rate, growth retardation, reduction in seed germination, biomass, leaf number, root elongation, and even plant death.
Chapter
Nanotechnology-based industries are projected to grow from a multimillion-dollar industry to a few billions of dollars in the next few decades. The rate of nanotechnology production is very high as per global market scenario. With increasing penetration of nanomaterials (NMs) in our daily lives through consumer products, nanowastes and nanobyproducts are bound to circulate in the environment and our surroundings. These include the byproducts generated from nanotechnology processed products. This chapter discusses the various NMs or nanostructured byproducts and the nanowaste that is generated by various industries. Nanoparticles that are released into the atmosphere are contemplate as different categories of waste when compared to their bulk counterpart. NMs recycling offers many benefits in both environmental and economic terms. NMs can be recycled from both new and pure products (from nanomanufacturing) and used products (nanowaste from nanointegrated products). This chapter discusses various processes of nanobyproduct generation and utilization that will be part of the evolution toward green technology.
Chapter
The applications of ILs in the preparation and recovery of several inorganic and hybrid materials are promising. ILs can be generally applied for several materials, such as metals, nonmetal elements, silicas, metal oxides, chalcogenides, and porous materials. ILs offer high recyclability and can be cost-effective after optimization, making them attractive and receiving a growing number of scientists. ILs can be considered green solvents. The methods that implement ILs are sustainable and could be effective in comparison to conventional methods. Future research will explore the synthesis of cheap ILs, making use of cost-effective methods.
Chapter
Full-text available
Toxicity of nanoparticles in the aquatic environment is of serious concern as increasing concentration of nanoparticles potentially affects the aquatic plants and animals living in the aquatic ecosystem. Engineered nanoparticles (ENPs) are derived from anthropogenic sources, which are highly stable and uniform in distribution. In the aquatic environment, there is an alarming situation and indefinite safety use for the ENPs. The ENPs interact with aquatic organisms at trophic levels (lower and upper levels) throughout the aquatic food chain. Advancement is rendered in the evaluation of bioaccumulation in recent years, and the transfer in trophic level of ENPs. While findings of numerous studies carried out in different locations of the world have proved the noxious consequences of nanomaterials upon the organism's in the aquatic environment as well as in what manner they impact food chain resulting in bioaccumulation, affecting marine animals’ wellbeing, development, reproduction, and physiology. We are exploring the nanotoxicity in the aquatic food chain and aquatic species, trophic transition, and biomagnification in this chapter. The critical points of the study are that ENPs are able to go up to three trophic stages in the aquatic food chain. Biomagnification of various nanoparticles (quantum dots, nAu, nCeO2 and nTiO2) fit for two trophic levels have a biomagnification ratio greater than one. Not many studies on the third trophic stage nevertheless demonstrated biomagnification. The deposition of ENPs in aquatic plants and animals has also been shown to affect physiological processes of different organisms.
Article
Full-text available
The use of Carbon Nanotubes (CNT) and Graphene increased in the last decade and it is likely to keep increasing in the near future. The attractiveness of their properties, particularly the possibility to enhance the composites performance using a tailor made methodology, brings new materials, processes and products for highly demanding industrial applications and to the market. However, there are quite a lot of health/safety issues, as well as lack of understanding and standards to evaluate their effects. This paper starts with a general description of materials, processes and products dealing with CNT and graphene. Then, an overview of concerns related to the health and safety when handling, researching, producing and using products that include these materials is presented. It follows a risk management approach with respect to simulation and evaluation tools, and considering the consensual limits already existing for research, industry and consumers. A general discussion integrating the relevant aspects of health and safety with respect to CNT and graphene is also presented. A proactive view is presented with the intention to contribute with some guidelines on installation, maintenance, evaluation, personal protection equipment (PPE) and personnel training to deal with these carbon-based nanomaterials in research, manufacture, and use with composite materials.
Article
Full-text available
Atopic dermatitis (AD) is a predominant and deteriorating chronic inflammation of the skin, categorized by robust burning and eczematous lacerations in diverse portions of the body. AD affects about 20% of both offspring and adults worldwide. The pathophysiology of AD combines environmental, hereditary, and immunological aspects, together with skin barrier dysfunction. The procedures used to prevent the disease are the everyday usage of creams to support the restoration of the epidermal barrier. The classical treatments include the use of topical corticosteroids as a first-line therapy, but also calcineurin inhibitors, antihistamines, antibiotics, phototherapy, and also immunosuppressant drugs in severe cases of AD. Topical drug delivery to deeper skin layers is a difficult task due to the skin anatomic barrier, which limits deeper penetration of drugs. Groundbreaking drug delivery systems, based on nanoparticles (NPs), have received much attention due to their ability to improve solubility, bioavailability, diffusion, targeting to specific types of cells, and limiting the secondary effects of the drugs employed in the treatment of AD. Even so, additional studies are still required to recognize the toxicological characteristics and long-term safety of NPs. This review discusses the current classical pharmacotherapy of AD against new nanoparticle skin delivery systems and their toxicologic risks.
Article
Full-text available
The methods of laser confocal microscopy were employed to study the changes in rat target organs (iliac mucosa and liver) provoked by peroral administration of dispersion of nanosized (31 nm) multimolecular fullerene C60 particles in doses of 0.1, 1.0, and 10 mg/kg body weight over 92 days. The micropreparations were selectively stained with fluorescent dyes to mark the cell nuclei (DAPI), actin microfilaments (fluorescently labeled phalloidin), and the membrane proteins CD106, CD31, and claudins in tight junctions (fluorescently labeled monoclonal antibodies). In rats treated with fullerene in the examined doses, the iliac mucosa demonstrated normal morphology of the villi. There were no signs of inflammation and no alterations in the actin fi laments of cytoskeleton and in enterocytic tight junctions. The count of CD106(+) and CD31(+) cells did not change. The highest examined doses of fullerene (1 and 10 mg/kg body weight) increased population and modified distribution of hepatic CD106(+) cells. They also resulted in accumulation of cytoplasmic granules presumably identified as Kupffer macrophages without any signs of visible inflammation or necrotic areas. This phenomenon can reflect the early stages of toxic reaction being a sensitive bioindicator of the damage produced by administered fullerene C60 in the hepatic tissue.
Article
Full-text available
Important challenges in the global water situation, mainly resulting from worldwide population growth and climate change, require novel innovative water technologies in order to ensure a supply of drinking water and reduce global water pollution. Against this background, the adaptation of highly advanced nanotechnology to traditional process engineering offers new opportunities in technological developments for advanced water and wastewater technology processes. Here, an overview of recent advances in nanotechnologies for water and wastewater treatment processes is provided, including nanobased materials, such as nanoadsorbents, nanometals, nanomembranes, and photocatalysts. The beneficial properties of these materials as well as technical barriers when compared with conventional processes are reported. The state of commercialization is presented and an outlook on further research opportunities is given for each type of nanobased material and process. In addition to the promising technological enhancements, the limitations of nanotechnology for water applications, such as laws and regulations as well as potential health risks, are summarized. The legal framework according to nanoengineered materials and processes that are used for water and wastewater treatment is considered for European countries and for the USA.
Article
Full-text available
Multi-walled carbon nanotubes (MWCNT) are an inhomogeneous group of nanomaterials that vary in lengths, shapes and types of metal contamination, which makes hazard evaluation difficult. Here we present a toxicogenomic analysis of female C57BL/6 mouse lungs following a single intratracheal instillation of 0, 18, 54 or 162μg/mouse of a small, curled (CNTSmall, 0.8±0.1μm in length) or large, thick MWCNT (CNTLarge, 4±0.4μm in length). The two MWCNT were extensively characterized by SEM and TEM imaging, thermograviometric analysis, and Brunauer-Emmett-Teller surface area analysis. Lung tissues were harvested 24hours, 3days and 28days post-exposure. DNA microarrays were used to analyze gene expression, in parallel with analysis of bronchoalveolar lavage fluid, lung histology, DNA damage (comet assay) and the presence of reactive oxygen species (dichlorodihydrofluorescein assay), to profile and characterize related pulmonary endpoints. Overall changes in global transcription following exposure to CNTSmall or CNTLarge were similar. Both MWCNT elicited strong acute phase and inflammatory responses that peaked at day 3, persisted up to 28days, and were characterized by increased cellular influx in bronchoalveolar lavage fluid, interstitial pneumonia and gene expression changes. However, CNTLarge elicited an earlier onset of inflammation and DNA damage, and induced more fibrosis and a unique fibrotic gene expression signature at day 28, compared to CNTSmall. The results indicate that the extent of change at the molecular level during early response phases following an acute exposure is greater in mice exposed to CNTLarge, which may eventually lead to the different responses observed at day 28. Copyright © 2014. Published by Elsevier Inc.
Article
Full-text available
The discovery of the nanoworld in the past decade or so has depended to a large extent on the invention of the atomic force microscope and a variety of methods to fabricate nanostructures.
Article
Full-text available
Carbon nanotubes functionalized with biological molecules (such as protein peptides and nucleic acids) show great potential for application in bioengineering and nanotechnology. Fundamental understanding, description, and regulation of such bio-nano-systems will ultimately lead to a new generation of integrated systems that combine unique properties of the carbon nanotube (CNT) with biological recognition capabilities. In this review, we describe recent advances in understanding the interactions between deoxyribonucleic acids (DNA) and CNT, as well as relevant simulation techniques. We also review progress in simulating DNA noncovalent interactions with CNTs in an aqueous environment. Molecular dynamics simulations indicate that DNA molecules may be encapsulated inside or wrap around CNT owing to van der Waals attraction between DNA and CNT. We focus on the dynamics and energetics of DNA encapsulation inside nanotubes and discuss the mechanism of encapsulation and the effects of nanotube size, nanotube end-group, DNA base sequence, solvent temperature and pressure on the encapsulation process. Finally, we discuss the likely impact of DNA encapsulation on bioengineering and nanotechnology, as well as other potential applications.
Article
Full-text available
Nanoparticles are increasingly being recognized for their potential utility in biological applications including nanomedicine. Here we examine the response of normal human cells to ZnO nanoparticles under different signaling environments and compare it to the response of cancerous cells. ZnO nanoparticles exhibit a strong preferential ability to kill cancerous T cells (~28–35 ×) compared to normal cells. Interestingly, the activation state of the cell contributes toward nanoparticle toxicity, as resting T cells display a relative resistance while cells stimulated through the T cell receptor and CD28 costimulatory pathway show greater toxicity in direct relation to the level of activation. Mechanisms of toxicity appear to involve the generation of reactive oxygen species, with cancerous T cells producing higher inducible levels than normal T cells. In addition, nanoparticles were found to induce apoptosis and the inhibition of reactive oxygen species was found to be protective against nanoparticle induced cell death. The novel findings of cell selective toxicity, towards potential disease causing cells, indicate a potential utility of ZnO nanoparticles in the treatment of cancer and/or autoimmunity.
Article
Full-text available
We review the recent progress in our understanding of the mechani-cal and electrical properties of carbon nanotubes, emphasizing the theoretical aspects. Nanotubes are the strongest materials known, but the ultimate limits of their strength have yet to be reached experimentally. Modeling of nanotube-reinforced composites indicates that the addition of small numbers of nanotubes may lead to a dramatic increase in the modulus, with only minimal crosslinking. Deformations in nanotube structures lead to novel structural transformations, some of which have clear electrical signatures that can be utilized in nanoscale sensors and devices. Chemical reactiv-ity of nanotube walls is facilitated by strain, which can be used in processing and functionalization. Scanning tunneling microscopy and spectroscopy have provided a wealth of information about the structure and electronic properties of nanotubes, espe-cially when coupled with appropriate theoretical models. Nanotubes are exceptional ballistic conductors, which can be used in a variety of nanodevices that can operate at room temperature. The quantum transport through nanotube structures is reviewed at some depth, and the critical roles played by band structure, one-dimensional con-finement, and coupling to nanoscale contacts are emphasized. Because disorder or point defect–induced scattering is effectively averaged over the circumference of the nanotube, electrons can propagate ballistically over hundreds of nanometers. How-ever, severe deformations or highly resistive contacts isolate nanotube segments and lead to the formation of quantum dots, which exhibit Coulomb blockade effects, even at room temperature. Metal-nanotube and nanotube-nanotube contacts range from highly transmissive to very resistive, depending on the symmetry of two struc-tures, the charge transfer, and the detailed rehybridization of the wave functions. The progress in terms of nanotube applications has been extraordinarily rapid, as evi-denced by the development of several nanotube-based prototypical devices, including memory and logic circuits, chemical sensors, electron emitters and electromechanical actuators.
Article
Full-text available
Over the past decade, there has been an increasing interest in using nanotechnology for cancer therapy. The development of smart targeted nanoparticles (NPs) that can deliver drugs at a sustained rate directly to cancer cells may provide better efficacy and lower toxicity for treating primary and advanced metastatic tumors. We highlight some of the promising classes of targeting molecules that are under development for the delivery of NPs. We also review the emerging technologies for the fabrication of targeted NPs using microfluidic devices.
Article
Full-text available
In reduced dimensions, materials display characteristics quite different from their bulk behavior. Interestingly, most viruses, bacteria, pathogens, particles in gas phase and other chemical–biological agents, which form the basis of this investigation, also have comparable dimensions. Our present and ongoing investigation is aimed towards the detection of chemical and biological agents using nanostructured materials. We have studied nanotubes, nanoparticles, nanowires, and nanoporous materials for biocompatibility and subsequent detection. In addition, based on our field emission studies on carbon nanotubes, we have suggested device designs to detect environmental emission. Detection strategies and preliminary data from electrochemical sensors, atomic force microscopy, and surface plasmon resonance are presented for the detection of chemical–biological agents immobilized on layers of nanoparticles. As a critical step in the development of sensors/detectors, strategies for surface functionalization and immobilization for carbon nanostructures, nanoparticles, and nanoporous materials are also presented. Such devices display unique characteristics, morphological flexibility, and biocompatibility. The eventual objective of our investigation is to develop a nanotechnology based sensor platform that will enable the direct electrical, optical, or electro-optical detection of biological and chemical agents in a label-free, highly multiplexed format over a broad dynamic range.
Article
Full-text available
The toxicity of carbon nanotubes is the subject of ongoing debate. A preliminary study using a small number of mice shows that they may be safe, but the results should be treated with caution.
Article
Full-text available
The interactions between neutral Al12X(I h ) (X = Al, C, N and P) nanoparticles and DNA nucleobases, namely adenine (A), thymine (T), guanine (G) and cytosine (C), as well as the Watson−Crick base pairs (BPs) AT and GC, were investigated by means of density functional theory computations. The Al12X clusters can tightly bind to DNA bases and BPs to form stable complexes with negative binding Gibbs free energies at room temperature, and considerable charge transfers occur between the bases/BPs and the Al12X clusters. These strong interactions, which are also expected for larger Al nanoparticles, may have potentially adverse impacts on the structure and stability of DNA and thus cause its dysfunction. Figure Adenine–thymine complex with aluminium Al12X nanoparticle
Article
Full-text available
Ultrafine particles or nanoparticles (UFPs or PM0.1) are the fraction of ambient particulates with an aerodynamic diameter smaller than 0.1 microm. Currently UFPs are emerging as the most abundant particulate pollutants in urban and industrial areas, as their exposures have increased dramatically because of anthropogenic sources such as internal combustion engines, power plants, incinerators and many other sources of thermo-degradation. Ultrafine particles have been less studied than PM2.5 and PM10 particulates, mass concentrations of particles smaller than 2.5 and 10 microm, respectively. OBJECTIVE, EVIDENCE AND INFORMATION SOURCES: We examined the current scientific literature about the health effects of ultrafine particles exposure. UFPs are able to inhibit phagocytosis, and to stimulate inflammatory responses, damaging epithelial cells and potentially gaining access to the interstitium. They could be responsible for consistent reductions in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) in patients with asthma. Chronic exposure to UFPs can produce deleterious effects on the lung, also causing oxidative stress and enhancing pro-inflammatory effects in airways of COPD patients. Cardiovascular detrimental consequences due to UFPs exposure have observed in epidemiological studies, and could likely be explained by translocation of UFPs from the respiratory epithelium towards circulation and subsequent toxicity to vascular endothelium; alteration of blood coagulation; triggering of autonomic nervous system reflexes eventually altering the cardiac frequency and function. Once deposited deeply into the lung, UFPs--in contrast to larger-sized particles--appear to access to the blood circulation by different transfer routes and mechanisms, resulting in distribution throughout the body, including the brain, with potential neurotoxic consequences. UFPs represent an area of toxicology of emerging concern. A new concept of environmental medicine would help in understanding not only the environmental mechanisms of disease, but also in developing specific preventive or therapeutic strategies for minimizing the dangerous influence of pollution on health.
Article
Full-text available
Nanomaterials are extensively used in industry and daily life, but little is known about possible health effects. An intensified research regarding toxicity of nanomaterials is urgently needed. Several studies have demonstrated that nanoparticles (NPs; diameter < 100 nm) can be transported to the central nervous system; however, interference of NPs with the electrical activity of neurons has not yet been shown. We investigated the acute electrophysiological effects of carbon black (CB), hematite (Fe2O3), and titanium dioxide (TiO2) NPs in primary murine cortical networks on microelectrode array (MEA) neurochips. Uptake of NPs was studied by transmission electron microscopy (TEM), and intracellular formation of reactive oxygen species (ROS) was studied by flow cytometry. The multiparametric assessment of electrical activity changes caused by the NPs revealed an NP-specific and concentration-dependent inhibition of the firing patterns. The number of action potentials and the frequency of their patterns (spike and burst rates) showed a significant particle-dependent decrease and significant differences in potency. Further, we detected the uptake of CB, Fe2O3, and TiO2 into glial cells and neurons by TEM. Additionally, 24 hr exposure to TiO2 NPs caused intracellular formation of ROS in neuronal and glial cells, whereas exposure to CB and Fe2O3 NPs up to a concentration of 10 µg/cm2 did not induce significant changes in free radical levels. NPs at low particle concentrations are able to exhibit a neurotoxic effect by disturbing the electrical activity of neuronal networks, but the underlying mechanisms depend on the particle type.
Article
Full-text available
Consider a single agent capable of diagnosing cancer, treating it simultaneously and monitoring response to treatment. Particles of this agent would seek cancer cells accurately and destroy them without harming normal surrounding cells. Science fiction or reality? Nanotechnology and nanomedicine are rapidly growing fields that encompass the creation of materials and devices at atomic, molecular and supramolecular level, for potential clinical use. Advances in nanotechnology are bringing us closer to the development of dual and multi-functional nanoparticles that are challenging the traditional distinction between diagnostic and treatment agents. Examples include contrast agents capable of delivering targeted drugs to specific epithelial receptors. This opens the way for targeted chemotherapy which could minimise systemic side-effects, avoid damage to benign tissues and also reduce the therapeutic treatment dose of a drug required. Most of the current research is still at the pre-clinical stage, with very few instances of bench to bedside research. In order to encourage more translational research, a fundamental change is required to consider the current clinical challenges and then look at ways in which nanotechnology can address these.
Article
Full-text available
A range of different particle types cause excessive lung inflammation that is thought to play a role in the various types of pathology they produce. Recently attention has been focused on ultrafine particles and the phenomenon of rat lung overload. The authors and their collaborators have shown previously that the surface area metric drives the overload response. Acute inflammatory response following instillation of particles has also been used to evaluate hazard but has been criticized because of the non-physiological delivery and the problems of local overload. We have instilled a number of low-toxicity dusts of various particle sizes and assessed neutrophil influx into the lung at 18–24 h. The extent of inflammation has been shown to be a function of the surface area instilled. Since ultrafine particles present a ‘special’ case of high surface area, they are relatively inflammogenic. There is no evidence that ultrafine particles of carbon black, titanium dioxide or latex have any special reactivity in addition to their large surface area. We tested whether we could use this approach to model the reactivity of highly toxic dusts. Rats were instilled with either DQ12 quartz or aluminium lactate-treated DQ12 and, as anticipated, the high specific surface toxicity of DQ12 meant that it was much more inflammogenic than was predicted using the relationship described for low-toxicity dusts. By contrast, aluminium lactate-treated DQ12 fell on to the line of ‘low-toxicity’ dusts. This approach presents the possibility of modelling potential toxicity for nuisance dusts based on the inflammatory response of a given instilled surface area dose.
Article
Full-text available
In the absence of scientific clarity about the potential health effects of occupational exposure to nanoparticles, a need exists for guidance in decision making about hazards, risks, and controls. An identification of the ethical issues involved may be useful to decision makers, particularly employers, workers, investors, and health authorities. Because the goal of occupational safety and health is the prevention of disease in workers, the situations that have ethical implications that most affect workers have been identified. These situations include the a) identification and communication of hazards and risks by scientists, authorities, and employers; b) workers' acceptance of risk; c) selection and implementation of controls; d) establishment of medical screening programs; and e) investment in toxicologic and control research. The ethical issues involve the unbiased determination of hazards and risks, nonmaleficence (doing no harm), autonomy, justice, privacy, and promoting respect for persons. As the ethical issues are identified and explored, options for decision makers can be developed. Additionally, societal deliberations about workplace risks of nanotechnologies may be enhanced by special emphasis on small businesses and adoption of a global perspective.
Article
Full-text available
Stuart C McBain, Humphrey HP Yiu, Jon DobsonInstitute of Science and Technology in Medicine, Keele University, Thornburrow Drive, Hartshill, Stoke-on-Trent, Staffordshire, ST4 7QB, U.K.Abstract: Investigations of magnetic micro- and nanoparticles for targeted drug delivery began over 30 years ago. Since that time, major progress has been made in particle design and synthesis techniques, however, very few clinical trials have taken place. Here we review advances in magnetic nanoparticle design, in vitro and animal experiments with magnetic nanoparticle-based drug and gene delivery, and clinical trials of drug targeting.Keywords: magnetic nanoparticles, gene delivery, biotechnology
Article
Full-text available
We conducted a series of experiments with ultrafine particles (approximately 20 nm) and larger particles (less than 200 nm) of "nuisance" dusts to evaluate the involvement of alveolar macrophages (AM) in particle-induced lung injury and particle translocation in rats. After intratracheal instillation of both ultrafine particles and larger particles of TiO2, we found a highly increased interstitial access of the ultrafine particles combined with a large acute inflammatory reaction as determined by lung lavage parameters. An additional experiment revealed that intratracheal instillation of phagocytized ultrafine TiO2 particles (inside AM) prevented both the pulmonary inflammatory reaction and the interstitial access of the ultrafine particles. Another experiment showed that the influx of polymorphonuclear cells (PMN) into the alveolar space unexpectedly decreased with higher doses of ultrafine particles, whereas alveolar epithelial permeability (protein leakage) increased. The divergence between PMN influx into the alveolar space and changes in alveolar epithelial permeability implies that they are separate events. Pulmonary inflammatory parameters determined by lung lavage analysis correlated best with the surface area of the retained particles rather than with their mass, volume, or numbers. Because higher doses resulted in an increased interstitialized fraction of particles, we suggest that inflammatory events induced by particles in the interstitial space can modify the inflammation in the alveolar space detectable by lung lavage. Our results demonstrate the dual role of AM for modifying particle-induced lung injury, i.e., both preventing such injury and contributing to it. We conclude that the increased pulmonary toxicity of ultrafine particles is related to their larger surface area and to their increased interstitial access.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Based on fundamental chemistry, biotechnology and materials science have developed over the past three decades into today's powerful disciplines which allow the engineering of advanced technical devices and the industrial production of active substances for pharmaceutical and biomedical applications. This review is focused on current approaches emerging at the intersection of materials research, nanosciences, and molecular biotechnology. This novel and highly interdisciplinary field of chemistry is closely associated with both the physical and chemical properties of organic and inorganic nanoparticles, as well as to the various aspects of molecular cloning, recombinant DNA and protein technology, and immunology. Evolutionary optimized biomolecules such as nucleic acids, proteins, and supramolecular complexes of these components, are utilized in the production of nanostructured and mesoscopic architectures from organic and inorganic materials. The highly developed instruments and techniques of today's materials research are used for basic and applied studies of fundamental biological processes.
Article
Based on fundamental chemistry, biotechnology and materials science have developed over the past three decades into today's powerful disciplines which allow the engineering of advanced technical devices and the industrial production of active substances for pharmaceutical and biomedical applications. This review is focused on current approaches emerging at the intersection of materials research, nanosciences, and molecular biotechnology. This novel and highly interdisciplinary field of chemistry is closely associated with both the physical and chemical properties of organic and inorganic nanoparticles, as well as to the various aspects of molecular cloning, recombinant DNA and protein technology, and immunology. Evolutionary optimized biomolecules such as nucleic acids, proteins, and supramolecular complexes of these components, are utilized in the production of nanostructured and mesoscopic architectures from organic and inorganic materials. The highly developed instruments and techniques of today's materials research are used for basic and applied studies of fundamental biological processes.
Article
PBPK modeling with alkenes has led to consideration of primary metabolites, oxiranes that are sufficiently stable to be distributed from sites of production to more remote tissues in the body. These oxiranes are cleared by epoxide hydrolase and by GSH conjugation. The successful modeling of most members of these classes of volatile organics revolves around the integration of multiple competing metabolic pathways on regulating the concentrations of toxic compounds that occur in the metabolic pathways. Benzene, an animal and human carcinogen with an uncertain mechanism of action, is a toxicologically important aromatic that undergoes oxidation of the ring double bonds to produce biologically active metabolites. Though there is some evidence that styrene in a carcinogen, non-carcinogenic endpoints, particularly acute effects, have motivated the development of several styrene models. For benzene and styrene, early PBPK models were typically simple, but were followed by more complex models based on more detailed descriptions of their metabolism. The interaction of multiple metabolites leads to important mixture issues even with exposures to benzene alone. A variety of model structures and strategies to incorporate aspects of the underlying biology and pharmacokinetics have been used throughout these PBPK models for alkenes and aromatics.
Article
Investigations of magnetic micro- and nanoparticles for targeted drug delivery began over 30 years ago. Since that time, major progress has been made in particle design and synthesis techniques, however, very few clinical trials have taken place. Here we review advances in magnetic nanoparticle design, in vitro and animal experiments with magnetic nanoparticle-based drug and gene delivery, and clinical trials of drug targeting.
Article
Rat inhalation experiments with titanium dioxide (TiO2) and barium sulfate (BaSO4), at concentrations calculated to produce similar volumetric lung burden for both dusts, showed overload with TiO2 but not for BaSO4. 'Overload,' occurring in rats exposed to 'low-toxicity' dusts at high concentrations, is characterized by a rapid deterioration in Clearance and onset of inflammation. Impairment of alveolar macrophage (AM) mediated clearance, dust translocation to the lymph nodes, and neutrophil (PMN) recruitment for both dusts were better predicted by the lung burden expressed as surface area rather than mass or volume. A mathematical model describing the translocation (in terms of particulate mass) of inhaled particles in various physiologically based pulmonary compartments was used to calculate pulmonary clearance when effective and also when impairment by overload leads to increased dust translocation to the lymph nodes. Our objectives were: (1) to modify this model to include the influence of particle surface area on clearance and interstitialization; (2) to extend the model to describe the PMN recruitment; and (3) to use the model to estimate the highest exposure level such that overload would be avoided in a chronic inhalation experiment with rats. In extrapolating down to no-overload concentrations, due account was taken of the observed interanimal variation (assuming this variation was mainly due to differences in inhaled dose). For TiO2 and BaSO4, with the given size distributions, the predicted concentrations at which 95% of the animals were expected to avoid overload were 3 mg m-3 and 7.5 mg m-3, respectively The general quantitative relationships on the role of particle surface area and on the estimation of the no-overload level have important implications for setting standards for poorly soluble particles.
Article
Based on fundamental chemistry, biotechnology and materials science have developed over the past three decades into today's powerful disciplines which allow the engineering of advanced technical devices and the industrial production of active substances for pharmaceutical and biomedical applications. This review is focused on current approaches emerging at the intersection of materials research, nanosciences, and molecular biotechnology. This novel and highly interdisciplinary field of chemistry is closely associated with both the physical and chemical properties of organic and inorganic nanoparticles, as well as to the various aspects of molecular cloning, recombinant DNA and protein technology, and immunology. Evolutionary optimized biomolecules such as nucleic acids, proteins, and supramolecular complexes of these components, are utilized in the production of nanostructured and mesoscopic architectures from organic and inorganic materials. The highly developed instruments and techniques of today's materials research are used for basic and applied studies of fundamental biological processes.
Article
Stem cells are a key element in tissue engineering and regenerative medicine. However, they require a suitable microenvironment to grow and regenerate. Carbon nanotubes (CNTs) have attracted much attention as promising materials for stem cell research due to their extraordinary properties, such as their extracellular matrix-like structure, high mechanical strength, optical properties, and high electrical conductivity. Of particular interest is the use of CNTs as biomimetic substrates to control the differentiation of stem cells. CNTs have also been combined with commonly used scaffolds to fabricate functional scaffolds to direct stem cell fate. CNTs can also be used for stem cell labeling due to their high optical absorbance in the near-infrared regime. In this paper, we review and discuss the applications of CNTs in stem cell research along with CNT toxicity issues.
Article
Groups of rats were exposed 6 h per day, 5 days per week for 12 weeks as follows: (1) control (filtered air); (2) TiO2-F (∼250 nm particle size); (3) TiO2-D (∼20 nm particle size); and (4) SiO2 (cristobalite, 800 nm particle size). At the end of exposure, retained lung burdens were 6.62 and 5.22 mg for TiO2-F and TiO2-D, respectively, and 0.34 mg for SiO2. Inflammatory parameters in lung lavage fluid (cells, protein, enzymes) were highly increased in the SiO2and TiO2-D group and only moderately in the TiO2-F group. Long-term lung clearance of85 Sr test particles, instilled or inhaled at the end of the dust exposures, was significantly prolonged in the SiO2and TiO2-D groups by factors of 28 and 8 and only moderately by a factor of 2 in the TiO2-F group compared to control. Pulmonary retention of TiO2-D particles was likewise highly increased whereas TiO2-F retention was less prolonged despite a slightly higher initial lung dust burden. We conclude, that inhalation of ultrafine particles of nuisance dusts can lead to increased pulmonary toxicity and that TLVs should be revised to take this into account.
Article
The electronic structure of small germanium, silicon, and carbon clusters is calculated. The calculation is carried out within a Hubbard-like Hamiltonian in which s- and p-electrons are taken into account. Charge transfer is allowed between the various atomic sites in order to achieve global charge neutrality. The local electronic density of states is calculated by means of the recursion method. The results for atomic aggregates with 20, 60 and 70 atoms are presented and compared with those obtained with other methods and with experimental data.
Article
Gold nanoparticles (Au NPs) have become one of the most interesting sensing materials because of their unique size- and shape-dependent optical properties, high extinction coefficients, and super-quenching capability. Au NPs that are bioconjugated with DNA (DNA-Au NPs) have been demonstrated for selective and sensitive detection ofanalytes such as mercury(II) ions, platelet-derived growth factor (PDGF), and adenosine triphosphate (ATP). This review focuses on approaches using DNA-Au NPs for colorimetric, fluorescent, and scattering detection ofbiopolymers and small solutes. We highlight the important roles that the size and concentration of Au NPs, the length and sequence of DNA, the nature of the capping agents, and the ionic strength and pH of solution play in determining the specificity and sensitivity of the nanosensors for the analytes. The advantages and disadvantages of different detection methods for sensing of interesting analytes using DNA-Au NPs will be discussed.
Article
Endohedral lanthanide metallofullerenes are new molecules that may have useful medicinal properties. In particular, endohedral holmium metallofullerenes have been utilized in a model metallofullerene radiotracer study. The 165Ho metallofullerenes were chemically functionalized to impart water solubility and then neutron activated to 166Ho in order to determine their biodistribution and metabolism properties. The results have been evaluated for potential applications of lanthanide metallofullerenes as new diagnostic or therapeutic radiopharmaceuticals. Use of metallofullerenes in conventional diagnostic radiology (MRI contrast and X-ray imaging agents) has also been considered.
Article
Based on fundamental chemistry, biotechnology and materials science have developed over the past three decades into today's powerful disciplines which allow the engineering of advanced technical devices and the industrial production of active substances for pharmaceutical and biomedical applications. This review is focused on current approaches emerging at the intersection of materials research, nanosciences, and molecular biotechnology. This novel and highly interdisciplinary field of chemistry is closely associated with both the physical and chemical properties of organic and inorganic nanoparticles, as well as to the various aspects of molecular cloning, recombinant DNA and protein technology, and immunology. Evolutionary optimized biomolecules such as nucleic acids, proteins, and supramolecular complexes of these components, are utilized in the production of nanostructured and mesoscopic architectures from organic and inorganic materials. The highly developed instruments and techniques of today's materials research are used for basic and applied studies of fundamental biological processes.
Article
We have observed thai nonderivatized C60 (buckminsterfullerene) could inhibit the replication of simian immunodeficiency virus (SIV) in vitro and the activity of Moloney murine leukemia virus (M-MuLV) reverse transcriptase (RT) (IC50 ≈3 μM). This means that biological effects are exerted via a direct and active interaction of the C6o skeleton with other macromolecules.
Article
Nanotechnology presents countless opportunities to develop new and improved consumer products for the benefit of society. However, as the industrial production and use of nanotechnology products continue to expand at a fast scale, potential human health concerns and ecological safeguards for the environment need to be addressed. Health risk assessment involving different animal species for multi-organ toxicity complimented with molecular investigations in cells is essential for investigating the potential toxic effects of nanomaterials. The purpose of this review is to present the current state of knowledge regarding the potential routes of human exposure to nanomaterials and their biological health effects. Although anthropogenic nanosized particles emitted in the environment are known to produce adverse human health in susceptible populations, much remains to be explored. Exposures can occur from direct exposure or from the use of commercial products made of nanomaterials. Safe manufacturing guidelines for prevention of exposures and recommendations on safe handling and use need to be established on a proactive basis to prevent adverse outcomes.
Article
In this study, the beneficial effect of an aqueous suspension of carbon nanopowder (CNP) in enhancing the efficiency of PCR (polymerase chain reaction) amplification was demonstrated for the first time in a repeated PCR and a long PCR system. For repeated PCR, the results showed that in the presence of a certain amount of CNP a predominant target DNA could be obtained even in the sixth round amplification, and that the high specificity is dependent on the concentration of CNP. It was also shown that the CNP significantly improved the amplification efficiency for long PCR reactions. Preliminary atomic force microscopy observation indicated that CNPr could directly bind with DNA molecule. Given that carbon nanotubes, carbon nanopowder, gold nanoparticles and some other types of nanoparticle are all capable for improving the PCR efficiency and/or binding with DNA, it is clear that there is space for PCR technology improvement in the context of some enhanced properties discovered from the introduction of nanoparticles into biological aqueous solution.
Article
Recent advances in nanotechnology have increased the development and production of many new nanomaterials with unique characteristics for industrial and biomedical uses. The size of these new nanoparticles (<100 nm) with their high surface area and unusual surface chemistry and reactivity poses unique problems for biological cells and the environment. This paper reviews the current research on the reactivity and interactions of carbon nanoparticles with biological cells in vivo and in vitro, with ultrastructural images demonstrating evidence of human cell cytotoxicity to carbon nanoparticles characteristic of lipid membrane peroxidation, gene down regulation of adhesive proteins, and increased cell death (necrosis, apoptosis), as well as images of nontoxic carbon nanoparticle interactions with human cells. Although it is imperative that nanomaterials be systematically tested for their biocompatibility and safety for industrial and biomedical use, there are now ways to develop and redesign these materials to be less cytotoxic, and even benign to cell systems. With this new opportunity to utilize the unique properties of nanoparticles for research, industry and medicine, there is a responsibility to test and optimize these new nanomaterials early during the development process, to eliminate or ameliorate identified toxic characteristics.
Article
We present a model for organic bistable devices (OBDs) embedded with metallic nanoparticles. The model takes into account charge transport through the organic material, field-dependent charge carrier mobility, and injection from the electrodes. The charge trapped by the nanoparticles induces space charge effects that reduce the electric field at the electrode and inhibit charge injection leading to the low conductivity state of the OBD. Between the two situations where the nanoparticles are neutral and charged with 15 units of charge, the ON-to-OFF ratio is more than two orders of magnitude. We also discuss the relevance of our model to various OBD devices in the literature.
Article
Structures, preparation, and physical properties of intrinsic polymeric fullerenes are reviewed. Three routes to the polymeric state are considered: polymerization by light, pressure, and charge transfer. For all three processes different types of polymers are known. Polymerization by charge transfer is discussed for AC60, A= K,Rb,Cs. The systems for Rb and Cs are quasi-1D metallic at room temperature. KC60 is either 3D metallic or phase separates into K3C60 and C60 Below 50 K RbC60 and CsC60 are insulators due to a spin density wave transition. The electron-phonon coupling for the molecular modes is unexpected low in the metallic state which is probably the reason for the lack of superconductivity in these systems.
Article
As the fullerene studies progress, two trends become more visible: the incorporation of the smaller cages of C60 type into organic chemistry and the increasing interest in the elongated fullerene species, carbon nanotubes. The latter turn out to be of interest for structural materials and for the submicro-electronics application. The mechanical strength of these molecular fibers combines with electronic properties, that are uniquely tunable by the molecular symmetry of nanotubes. We outline the basic features of fullerene nanotubes and the more recent findings in their mechanical and electrical properties.
Article
The field of atomic-resolution transmission electron microscopy and its application to materials science is reviewed. This technique, whose spatial resolution is now about one Angstrom, is valuable wherever nanoscale characterization of materials is needed. The history of the subject is briefly outlined, followed by a discussion of experimental techniques. Resolution-limiting factors are summarized, together with the underlying theory of image formation. Seven promising approaches to super-resolution are reviewed. The statistical principles of quantitative image analysis and defect modelling are outlined for both HREM and STEM. Methods for obtaining defect energies from images are discussed. The review ends with a summary of some recent applications, including such topics as the Fullerenes, nanotubes, dislocation kink imaging, superconductors, atomic-resolution imaging of whole semiconductor devices, the study of atomic defects in mediating first-order phase transitions, collosal magnetoresistance, ceramic interfaces, quasicrystals, imaging of surfaces, glasses, catalysts and magnetic materials.
Article
This review is introduced by an examination of the historical roles that quantized building blocks, such as atoms and monomers have played in the development of small molecule and traditional polymer synthesis, respectively. The unique features of traditional macromolecular architectures (i.e. linear, crosslinked, branched), as well as controlled nanostructures in biology were used as frames of reference to anticipate potential new properties, phenomena and synthetic constructs that should be expected to emerge at the interface of the ‘dendritic architectural state’ with the nanotechnology revolution. Intrinsic new properties associated with the ‘dendritic architectural state’, such as the ability to control monodisperse nanoscale sizes, shapes and presentation of surface functionality are reviewed. Unique ‘dendritic effects’ related to de Gennes dense packing (i.e. unimolecular encapsulation, periodic nanocontainer properties), polyvalency (nanoscaffolding), as well as shape designing both within (i.e. cystamine core dendrimers) and beyond dendrimers (i.e. core–shell tecto(dendrimers)) to mimic biological proteins are described. The precise, quantized core–shell architectural properties and monomer shell filling features of dendrimers are compared to the electron shell filling patterns of elemental atoms by utilizing the Niels Bohr Periodic Table. This comparison has provided a rationale for explaining autoreactivity patterns observed at the sub-nanoscale (atoms), lower nanoscale (dendrimers) and higher nanoscale levels involving either unsaturated electron shells, monomer shells or dendrimer shells, respectively. Clearly, dendritic polymers, especially dendrons and dendrimers are expected to fulfill important roles as fundamental, reactive modules for nanoscale polymer syntheses.
Article
Nanotechnology has enabled the development of an amazing variety of methods for fabricating nanotopography and nanopatterned chemistry in recent years. Some of these techniques are directed towards producing single component particles, as well as multi-component assembly or self-assembly. Other methods are aimed at nanofeaturing and patterning surfaces that have a specific chemistry or topography. This article concentrates mainly on surface-directed nanobiotechnologies because they are nearer to commercial realisation, such as use in tissue engineering, control of biofouling and cell culture, than those directed at producing nanoparticles.
Article
The preparation of a new type of finite carbon structure consisting of needlelike tubes is reported. Produced using an arc-discharge evaporation method similar to that used for fullerene sythesis, the needles grow at the negative end of the electrode used for the arc discharge. Electron microscopy reveals that each needle comprises coaxial tubes of graphitic sheets ranging in number from two up to about 50. On each tube the carbon-atom hexagons are arranged in a helical fashion about the needle axis. The helical pitch varies from needle to needle and from tube to tube within a single needle. It appears that this helical structure may aid the growth process. The formation of these needles, ranging from a few to a few tens of nanometers in diameter, suggests that engineering of carbon structures should be possible on scales considerably greater than those relevant to the fullerenes.
Article
Polyalkylsulfonated C60, or FC4S, a highly water-soluble caged fullerene derivative, is believed to be a free radical remover or an antioxidant in biological systems. A 50 mg/ml aqueous solution was prepared as a master solution and administered to female Sprague-Dawley CD(Crl:CD(SD)BR) rats in a single-dose acute toxicity study or a 12-day subacute toxicity study where rats were given the solution daily. In a study of the median lethal dose (LD50), no rats died after oral administration, and thus FC4S was considered to be nontoxic if administered orally. In an LD50 intraperitoneal injection study, rats died within 30 hr after injection; the LD50 was determined to be approximately 600 mg per kilogram of body weight. Rats injected with the compound intraperitoneally or intravenously immediately eliminated the compound through the kidney; the kidney appeared to be the primary target organ. The compound induced a distinct lysosome-overload nephrosis, a phagolysosomal nephropathy characterized by a tinctorial difference between the outer cortex and the inner cortex and the medulla. The affected outer cortex showed a diffuse degeneration, with the presence of numerous large vacuoles and cytoplasmic aggregates in the tubular epithelium. The phagolysosomal nephropathy was detected in rats after acute exposure as well as in the surviving rats following 1 intraperitoneal injection of 500 mg/kg or intravenous injection of 100 mg/kg. Ultrastructural investigation revealed numerous membranous conglomerates characteristic of phagolysosomal and/or lysosomal inclusions in the cytoplasm of the renal tubular epithelium. These conglomerates were confined to the vacuole, electron-dense, and unevenly stained. They varied in size and shape and were fused or aggregated. Occasional phagolysosomes were also observed in the endothelial cells of the peritubular plexus. A preliminary study of microsomal enzyme activity analysis revealed a suppression effect of liver cytochrome P-450-dependent monooxygenase activities, including cytochrome P-450, cytochrome b5, and benzo(a)pyrene hydroxylase, but an increased level of kidney cytochrome P-450-dependent monooxygenase activities, including NADPH-cytochrome P-450 reductase. The significance of these enzyme alterations was not well determined. Further study is needed to clarify the correlation between the alterations of microsomal enzyme activity and the nephropathy of lysosomal overload-induced changes. These changes may serve as a biological marker in toxicity screening tests for this class of compound.
Article
Nanoscale materials can have cytotoxic effects. Here we present the first combined empirical and theoretical investigation of the influence of electrostatic attraction on nanoparticle cytotoxicity. Modeling electrostatic interactions between cells and 13 nm spheres of zinc oxide nanoparticles provided insight into empirically determined variations of the minimum inhibitory concentrations between four differently charged isogenic strains of Pseudomonas aeruginosa PAO1. We conclude that controlling the electrostatic attraction between nanoparticles and their cellular targets may permit the modulation of nanoparticle cytotoxicity.
Article
Dosimetry parameters such as deposition, clearance, retention, and translocation and dissolution of inhaled particles in and to different lung compartments may be important for the persistence of particles in the lung and may correlate with adverse pulmonary effects. We investigated such correlations using a model involving TiO2 particles of two particle sizes (20 nm diameter, ultrafine; 250 nm diameter, fine) of the same crystalline structure (anatase). A 12-week inhalation experiment in rats resulted in a similar mass deposition of the two particle types in the lower respiratory tract. The ultrafine particles elicited a persistently high inflammatory reaction in the lungs of the animals compared to the larger-sized particles. In the postexposure period (up to 1 year) retention in the alveolar space per se was not different between fine and ultrafine TiO2. However, the following differences between the particle types were noted: a significantly different total pulmonary retention, both quantitatively (significantly prolonged retention of the ultrafine TiO2) and qualitatively (increased translocation to the pulmonary interstitium and persistence there of the ultrafine TiO2); greater epithelial effects (Type II cell proliferation; occlusion of pores of Kohn) and the beginning of interstitial fibrotic foci with ultrafine TiO2; significant sustained impairment of alveolar macrophage function after ultrafine TiO2 exposure as measured by the clearance of test particles. A correlation between particle surface area and effects was observed. A comparison of the adverse reactions with dosimetric parameters of TiO2 in different lung compartments in the postexposure period showed a correlation of the persistence of effects in both the alveolar and interstitial space with the persistence of particles in the respective compartment.