Nanotoxicology is a sub-specialty of particle toxicology. It addresses the toxicology of nanoparticle (particles <100 nm diameter) which appear to have toxicity effects that are unusual and not seen with larger particles. Nanoparticles can be divided into combustion-derived nanoparticles (like diesel soot), manufactured nanoparticles like carbon nanotubes and naturally occurring nanoparticles from volcanic eruptions, atmospheric chemistry etc. Typical nanoparticles that have been studied are titanium dioxide, alumina, zinc oxide, carbon black, and carbon nanotubes, and "nano-C60". Nanoparticles seem to have some different properties from larger particles that are known to have pathogenic effects, like asbestos or quartz. These differences seem to be a result of their size. Nanoparticles have much larger surface area to unit mass ratios which in some cases may lead to greater pro-inflammatory effects (in, for example, lung tissue). In addition, some nanoparticles seem to be able to translocate from their site of deposition to distant sites such as the blood and the brain. This has resulted in a sea-change in how particle toxicology is viewed- instead of being confined to the lungs, nanoparticle toxicologists study the brain, blood, liver, skin and gut. Nanotoxicology has revolutionised particle toxicology and rejuvenated it.
The smaller a particle is, the greater its surface area to volume ratio and the higher its chemical reactivity and biological activity. The greater chemical reactivity of nanomaterials results in increased production of reactive oxygen species (ROS), including free radicals. ROS production has been found in a diverse range of nanomaterials including carbon fullerenes, carbon nanotubes and nanoparticle metal oxides. ROS and free radical production is one of the primary mechanisms of nanoparticle toxicity; it may result in oxidative stress, inflammation, and consequent damage to proteins, membranes and DNA
The extremely small size of nanomaterials also means that they much more readily gain entry into the human body than larger sized particles. How these nanoparticles behave inside the body is still a major question that needs to be resolved. The behavior of nanoparticles is a function of their size, shape and surface reactivity with the surrounding tissue. In principle, a large number of particles could overload the body's phagocytes, cells that ingest and destroy foreign matter, thereby triggering stress reactions that lead to inflammation and weaken the body’s defense against other pathogens. In addition to questions about what happens if non-degradable or slowly degradable nanoparticles accumulate in bodily organs, another concern is their potential interaction or interference with biological processes inside the body. Because of their large surface area, nanoparticles will, on exposure to tissue and fluids, immediately adsorb onto their surface some of the macromolecules they encounter. This may, for instance, affect the regulatory mechanisms of enzymes and other proteins.
Nanomaterials are able to cross biological membranes and access cells, tissues and organs that larger-sized particles normally cannot. Nanomaterials can gain access to the blood stream via inhalation or ingestion.At least some nanomaterials can penetrate the skin;even larger microparticles may penetrate skin when it is flexed. Broken skin is an ineffective particle barrier,suggesting that acne, eczema, shaving wounds or severe sunburn may accelerate skin uptake of nanomaterials. Then, once in the blood stream, nanomaterials can be transported around the body and be taken up by organs and tissues, including the brain, heart, liver, kidneys, spleen, bone marrow and nervous system.Nanomaterials have proved toxic to human tissue and cell cultures, resulting in increased oxidative stress, inflammatory cytokine production and cell death.Unlike larger particles, nanomaterials may be taken up by cell mitochondria and the cell nucleus. Studies demonstrate the potential for nanomaterials to cause DNA mutationn and induce major structural damage to mitochondria, even resulting in cell death.Size is therefore a key factor in determining the potential toxicity of a particle. However it is not the only important factor.
Other properties of nanomaterials that influence toxicity include: chemical composition, shape, surface structure, surface charge, aggregation and solubility, and the presence or absence of functional groups of other chemicals.The large number of variables influencing toxicity means that it is difficult to generalise about health risks associated with exposure to nanomaterials – each new nanomaterial must be assessed individually and all material properties must be taken into account.
Since there is no authority to regulate nanotech-based products, there are many products that could possibly be dangerous to humans. Scientific research has indicated the potential for some nanomaterials to be toxic to humans or the environment. In March 2004 tests conducted by environmental toxicologist Eva Oberdörster, Ph.D. working with Southern Methodist University in Texas, found extensive brain damage to fish exposed to fullerenes for a period of just 48 hours at a relatively moderate dose of 0.5 parts per million (commensurate with levels of other kinds of pollution found in bays). The fish also exhibited changed gene markers in their livers, indicating their entire physiology was affected. In a concurrent test, the fullerenes killed water fleas, an important link in the marine food chain.The extremely small size of fabricated nanomaterials also means that they are much more readily taken up by living tissue than presently known toxins. Nanoparticles can be inhaled, swallowed, absorbed through skin and deliberately or accidentally injected during medical procedures. They might be accidentally or inadvertently released from materials implanted into living tissue.
Researcher Shosaku Kashiwada of the National Institute for Environmental Studies in Tsukuba, Japan, in a more recent study, intended to further investigate the effects of nanoparticles on soft-bodied organisms. His study allowed him to explore the distribution of water-suspended fluorescent nanoparticles throughout the eggs and adult bodies of a species of fish, known as the see-through medaka (Oryzias latipes). See-through medaka were used because of their small size, wide temperature and salinity tolerances, and short generation time. Moreover, small fish like the see-through medaka have been popular test subjects for human diseases and organogenesis for other reasons as well, including their transparent embryos, rapid embryo development, and the functional equivalence of their organs and tissue material to that of mammals. Because the see-through medaka have transparent bodies, analyzing the deposition of fluorescent nanoparticles throughout the body is quite simple. For his study, Dr. Kashiwada evaluated four aspects of nanoparticle accumulation. These included the overall accumulation and the size-dependent accumulation of nanoparticles by medaka eggs, the effects of salinity on the aggregation of nanoparticles in solution and on their accumulation by medaka eggs, and the distribution of nanoparticles in the blood and organs of adult medaka. It was also noted that nanoparticles were in fact taken up into the bloodstream and deposited throughout the body. In the medaka eggs, there was a high accumulation of nanoparticles in the yolk; most often bioavailibility was dependent on specific sizes of the particles. Adult samples of medaka had accumulated nanoparticles in the gills, intestine, brain, testis, liver, and bloodstream. One major result from this study was the fact that salinity may have a large influence on the bioavailibility and toxicity of nanoparticles to penetrate membranes and eventually kill the specimen.
As the use of nanomaterials increases worldwide, concerns for worker and user safety are mounting. To address such concerns, the Swedish Karolinska Institute conducted a study in which various nanoparticles were introduced to human lung epithelial cells. The results, released in 2008, showed that iron oxide nanoparticles caused little DNA damage and were non-toxic. Zinc oxide nanoparticles were slightly worse. Titanium dioxide caused only DNA damage. Carbon nanotubes caused DNA damage at low levels. Copper oxide was found to be the worst offender, and was the only nanomaterial identified by the researchers as a clear health risk.
Immunogenicity to nanoparticles. Very few attention has been concentrated in the potential immunogenicity of nanostructures. Nanostructures can activate the immune system inducing inflammation, immune responses, allergy, or even affect to the immune cells in a deleterious or beneficial way(immunosuppression in autoinmmunity diseases, improving immune responses in vaccines). Many studies are needed in order to know the potential deleterous or beneficial effects of nanostructures in the immune system. Comparing to the conventional pharmeceutical agents, nanostructures has a huge size and immune cells, specially phagocytic cells, recognize and try to destroy them.
In addition, standarization of toxicology tests between laboratories are needed. Díaz, B. et al from the University of Vigo (Spain) has shown (Small, 2008) that many different cell lines should be studied in order to know if a nanostructure induces toxicity, and human cells can intenalize aggregated nanoparticles. Moreover, it is important to take into account that many nanostructures aggregate in biological fluids, but groups manufacturing nanostructures do not care much about this matter. Many efforts of interdisciplinary groups are strongly needed in order to progress in this field
Human health and safety
Calls for tighter regulation of nanotechnology have arisen alongside a growing debate related to the human health and safety risks associated with nanotechnology. The Royal Society identifies the potential for nanoparticles to penetrate the skin, and recommends that the use of nanoparticles in cosmetics be conditional upon a favorable assessment by the relevant European Commission safety advisory committee. Andrew Maynard 
also reports that ‘certain nanoparticles may move easily into sensitive lung tissues after inhalation, and cause damage that can lead to chronic breathing problems’.
Carbon nanotubes – characterized by their microscopic size and incredible tensile strength – are frequently likened to asbestos, due to their needle-like fiber shape. In a recent study that introduced carbon nanotubes into the abdominal cavity of mice, results demonstrated that long thin carbon nanotubes showed the same effects as long thin asbestos fibers, raising concerns that exposure to carbon nanotubes may lead to mesothelioma (cancer of the lining of the lungs caused by exposure to asbestos).Given these risks, effective and rigorous regulation has been called for to determine if, and under what circumstances, carbon nanotubes are manufactured, as well as ensuring their safe handling and disposal.The Woodrow Wilson Centre’s Project on Emerging Technologies conclude that there is insufficient funding for human health and safety research, and as a result there is currently limited understanding of the human health and safety risks associated with nanotechnology. While the US National Nanotechnology Initiative reports that around four percent (about $40 million) is dedicated to risk related research and development, the Woodrow Wilson Centre estimate that only around $11 million is actually directed towards risk related research. They argued in 2007 that it would be necessary to increase funding to a minimum of $50 million in the following two years so as to fill the gaps in knowledge in these areas.
The potential for workplace exposure was highlighted by the 2004 Royal Society report which recommended a review of existing regulations to assess and control workplace exposure to nanoparticles and nanotubes. The report expressed particular concern for the inhalation of large quantities of nanoparticles by workers involved in the manufacturing process.
Stakeholders concerned by the lack of a regulatory framework to assess and control risks associated with the release of nanoparticles and nanotubes have drawn parallels with bovine spongiform encephalopathy (‘mad cow’s disease), thalidomide, genetically modified food),) nuclear energy, reproductive technologies, biotechnology, and asbestosis light of such concerns, the Canadian based ETC Group have called for a moratorium on nano-related research until comprehensive regulatory frameworks are developed that will ensure workplace safety.
also reports that ‘certain nanoparticles may move easily into sensitive lung tissues after inhalation, and cause damage that can lead to chronic breathing problems’.Carbon nanotubes – characterized by their microscopic size and incredible tensile strength – are frequently likened to asbestos, due to their needle-like fiber shape. In a recent study that introduced carbon nanotubes into the abdominal cavity of mice, results demonstrated that long thin carbon nanotubes showed the same effects as long thin asbestos fibers, raising concerns that exposure to carbon nanotubes may lead to mesothelioma (cancer of the lining of the lungs caused by exposure to asbestos).Given these risks, effective and rigorous regulation has been called for to determine if, and under what circumstances, carbon nanotubes are manufactured, as well as ensuring their safe handling and disposal.The Woodrow Wilson Centre’s Project on Emerging Technologies conclude that there is insufficient funding for human health and safety research, and as a result there is currently limited understanding of the human health and safety risks associated with nanotechnology. While the US National Nanotechnology Initiative reports that around four percent (about $40 million) is dedicated to risk related research and development, the Woodrow Wilson Centre estimate that only around $11 million is actually directed towards risk related research. They argued in 2007 that it would be necessary to increase funding to a minimum of $50 million in the following two years so as to fill the gaps in knowledge in these areas.
The potential for workplace exposure was highlighted by the 2004 Royal Society report which recommended a review of existing regulations to assess and control workplace exposure to nanoparticles and nanotubes. The report expressed particular concern for the inhalation of large quantities of nanoparticles by workers involved in the manufacturing process.
Stakeholders concerned by the lack of a regulatory framework to assess and control risks associated with the release of nanoparticles and nanotubes have drawn parallels with bovine spongiform encephalopathy (‘mad cow’s disease), thalidomide, genetically modified food),) nuclear energy, reproductive technologies, biotechnology, and asbestosis light of such concerns, the Canadian based ETC Group have called for a moratorium on nano-related research until comprehensive regulatory frameworks are developed that will ensure workplace safety.
Nanorobotics Approaches
Biochip
Main article: Biochip
The joint use of nanoelectronics, photolithography, and new biomaterials, can be considered as a possible way to enable the required manufacturing technology towards nanorobots for common medical applications, such as for surgical instrumentation, diagnosis and drug delivery.Indeed, this feasible approach towards manufacturing on nanotechnology is a practice currently in use from the electronics industry.So, practical nanorobots should be integrated as nanoelectronics devices, which will allow tele-operation and advanced capabilities for medical instrumentation.
Main article: Biochip
The joint use of nanoelectronics, photolithography, and new biomaterials, can be considered as a possible way to enable the required manufacturing technology towards nanorobots for common medical applications, such as for surgical instrumentation, diagnosis and drug delivery.Indeed, this feasible approach towards manufacturing on nanotechnology is a practice currently in use from the electronics industry.So, practical nanorobots should be integrated as nanoelectronics devices, which will allow tele-operation and advanced capabilities for medical instrumentation.
Nubots:
Main article: DNA machine
Nubot is an abbreviation for "nucleic acid robots." Nubots are synthetic robotics devices at the nanoscale. Representative nubots include the several DNA walkers reported by Ned Seeman's group at NYU, Niles Pierce's group at Caltech, John Reif's group at Duke University, Chengde Mao's group at Purdue, and Andrew Turberfield group at the University of Oxford.
Positional nanoassembly:
Nanofactory Collaboration founded by Robert Freitas and Ralph Merkle in 2000, is a focused ongoing effort involving 23 researchers from 10 organizations and 4 countries that is developing a practical research agenda specifically aimed at developing positionally-controlled diamond mechanosynthesis and a diamondoid nanofactory that would be capable of building diamondoid medical nanorobots.
Bacteria based:
This approach proposes the use biological microorganisms, like Escherichia coli bacteria.Hence, the model uses a flagellum for propulsion purposes. The use of electromagnetic fields are normally applied to control the motion of this kind of biological integrated device, although has limited applications.
Open Technology:
A document with a proposal on nanobiotech development using open technology approaches has been addressed to the United Nations General Assembly. According to the document sent to UN, in the same way Linux and Open Source has in recent years accelerated the development of computer systems, a similar approach should benefit the society at large and accelerate nanorobotics development. The use of nanobiotechnology should be established as a human heritage for the coming generations, and developed as an open technology based on ethical practices for peaceful purposes. Open technology is stated as a fundamental key for such aim.
Main article: DNA machine
Nubot is an abbreviation for "nucleic acid robots." Nubots are synthetic robotics devices at the nanoscale. Representative nubots include the several DNA walkers reported by Ned Seeman's group at NYU, Niles Pierce's group at Caltech, John Reif's group at Duke University, Chengde Mao's group at Purdue, and Andrew Turberfield group at the University of Oxford.
Positional nanoassembly:
Nanofactory Collaboration founded by Robert Freitas and Ralph Merkle in 2000, is a focused ongoing effort involving 23 researchers from 10 organizations and 4 countries that is developing a practical research agenda specifically aimed at developing positionally-controlled diamond mechanosynthesis and a diamondoid nanofactory that would be capable of building diamondoid medical nanorobots.
Bacteria based:
This approach proposes the use biological microorganisms, like Escherichia coli bacteria.Hence, the model uses a flagellum for propulsion purposes. The use of electromagnetic fields are normally applied to control the motion of this kind of biological integrated device, although has limited applications.
Open Technology:
A document with a proposal on nanobiotech development using open technology approaches has been addressed to the United Nations General Assembly. According to the document sent to UN, in the same way Linux and Open Source has in recent years accelerated the development of computer systems, a similar approach should benefit the society at large and accelerate nanorobotics development. The use of nanobiotechnology should be established as a human heritage for the coming generations, and developed as an open technology based on ethical practices for peaceful purposes. Open technology is stated as a fundamental key for such aim.
Nanorobotics theory
Since nanorobots would be microscopic in size, it would probably be necessary for very large numbers of them to work together to perform microscopic and macroscopic tasks. These nanorobot swarms, both those which are incapable of replication (as in utility fog) and those which are capable of unconstrained replication in the natural environment (as in grey goo and its less common variants), are found in many science fiction stories, such as the Borg nanoprobes in Star Trek. The word "nanobot" (also "nanite", "nanogene", or "nanoant") is often used to indicate this fictional is an informal or even pejorative term to refer to the engineering concept of nanorobots. The word nanorobot is the correct technical term in the nonfictional context of serious engineering studies.[citation needed]
Some proponents of nanorobotics, in reaction to the grey goo scare scenarios that they earlier helped to propagate, hold the view that nanorobots capable of replication outside of a restricted factory environment do not form a necessary part of a purported productive nanotechnology, and that the process of self-replication, if it were ever to be developed, could be made inherently safe. They further assert that free-foraging replicators are in fact absent from their current plans for developing and using molecular manufacturing.
Some proponents of nanorobotics, in reaction to the grey goo scare scenarios that they earlier helped to propagate, hold the view that nanorobots capable of replication outside of a restricted factory environment do not form a necessary part of a purported productive nanotechnology, and that the process of self-replication, if it were ever to be developed, could be made inherently safe. They further assert that free-foraging replicators are in fact absent from their current plans for developing and using molecular manufacturing.
Algorithmic self-assembly
DNA nanotechnology has been applied to the related field of DNA computing. A DX array has been demonstrated whose assembly encodes an XOR operation, which allows the DNA array to implement a cellular automaton which generates a fractal called the Sierpinski gasket. This shows that computation can be incorporated into the assembly of DNA arrays, increasing its scope beyond simple periodic arrays.
Note that DNA computing overlaps with, but is distinct from, DNA nanotechnology. The latter uses the specificity of Watson-Crick basepairing to make novel structures out of DNA. These structures can be used for DNA computing, but they do not have to be. Additionally, DNA computing can be done without using the types of molecules made possible by DNA Nanotechnology
Note that DNA computing overlaps with, but is distinct from, DNA nanotechnology. The latter uses the specificity of Watson-Crick basepairing to make novel structures out of DNA. These structures can be used for DNA computing, but they do not have to be. Additionally, DNA computing can be done without using the types of molecules made possible by DNA Nanotechnology
DNA nanotechnology
DNA nanotechnology makes use of branched DNA structures to create DNA complexes with useful properties. DNA is normally a linear molecule, in that its axis is unbranched. However, DNA molecules containing junctions can also be made. For example, a four-arm junction can be made using four individual DNA strands which are complementary to each other in the correct pattern. Due to Watson-Crick base pairing, only portions of the strands which are complementary to each other will attach to each other to form duplex DNA. This four-arm junction is an immobile form of a Holliday junction.
Junctions can be used in more complex molecules. The most important of these is the "double-crossover" or DX motif. Here, two DNA duplexes lie next to each other, and share two junction points where strands cross from one duplex into the other. This molecule has the advantage that the junction points are now constrained to a single orientation as opposed to being flexible as in the four-arm junction. This makes the DX motif suitible as a structural building block for larger DNA complexes.
Junctions can be used in more complex molecules. The most important of these is the "double-crossover" or DX motif. Here, two DNA duplexes lie next to each other, and share two junction points where strands cross from one duplex into the other. This molecule has the advantage that the junction points are now constrained to a single orientation as opposed to being flexible as in the four-arm junction. This makes the DX motif suitible as a structural building block for larger DNA complexes.
Origins
The first use of the concepts found in 'nano-technology' (but pre-dating use of that name) was in "There's Plenty of Room at the Bottom," a talk given by physicist Richard Feynman at an American Physical Society meeting at Caltech on December 29, 1959. Feynman described a process by which the ability to manipulate individual atoms and molecules might be developed, using one set of precise tools to build and operate another proportionally smaller set, and so on down to the needed scale. In the course of this, he noted, scaling issues would arise from the changing magnitude of various physical phenomena: gravity would become less important, surface tension and van der Waals attraction would become increasingly more significant, etc. This basic idea appeared plausible, and exponential assembly enhances it with parallelism to produce a useful quantity of end products. The term "nanotechnology" was defined by Tokyo Science University Professor Norio Taniguchi in a 1974 paper as follows: "'Nano-technology' mainly consists of the processing of, separation, consolidation, and deformation of materials by one atom or by one molecule." In the 1980s the basic idea of this definition was explored in much more depth by Dr. K. Eric Drexler, who promoted the technological significance of nano-scale phenomena and devices through speeches and the books Engines of Creation: The Coming Era of Nanotechnology (1986) and Nanosystems: Molecular Machinery, Manufacturing, and Computation,[and so the term acquired its current sense. Engines of Creation: The Coming Era of Nanotechnology is considered the first book on the topic of nanotechnology. Nanotechnology and nanoscience got started in the early 1980s with two major developments; the birth of cluster science and the invention of the scanning tunneling microscope (STM). This development led to the discovery of fullerenes in 1985 and carbon nanotubes a few years later. In another development, the synthesis and properties of semiconductor nanocrystals was studied; this led to a fast increasing number of metal and metal oxide nanoparticles and quantum dots. The atomic force microscope (AFM or SFM) was invented six years after the STM was invented. In 2000, the United States National Nanotechnology Initiative was founded to coordinate Federal nanotechnology research and development
