6. What are potential harmful effects of nanoparticles?
- 6.1 Can nanoparticles interact with living organisms?
- 6.2 Which characteristics of nanoparticles are relevant for health effects?
- 6.3 How can inhaled nanoparticles affect health?
- 6.4 What are the health implications of nanoparticles used as drug carriers?
- 6.5 How should harmful effects of nanoparticles be assessed?
- 6.6 What are the effects of nanoparticles on the environment?
6.1 Can nanoparticles interact with living organisms?
Nanoparticles, can have the same dimensions as biological molecules such as proteins.
In living systems, they may immediately adsorb onto their surface some of the large molecules they encounter as they enter the tissues and fluids of the body.
This ability of nanoparticles to have molecules “sticking” to their surface depends on the surface characteristics of the particles and can be relevant for drug delivery uses. Indeed, it is possible to deliver a drug directly to a specific cell in the body by designing the surface of a nanoparticle so that it adsorbs specifically onto the surface of the target cell.
But the interaction with living systems is also affected by the dimensions of the nanoparticles. For instance, nanoparticles no bigger than a few nanometres may reach well inside biomolecules, which is not possible for larger nanoparticles. Nanoparticles may cross cell membranes. It has been reported that inhaled nanoparticles can reach the blood and may reach other target sites such as the liver, heart or blood cells.
Key factors in the interaction with living structures include nanoparticle dose, the ability of nanoparticles to spread within the body, as well as their solubility. Some nanoparticles dissolve easily and their effects on living organisms are the same as the effects of the chemical they are made of. However, other nanoparticles do not degrade or dissolve readily. Instead, they may accumulate in biological systems and persist for a long time, which makes such nanoparticles of particular concern.
There remain many unknown details about the interaction of nanoparticles and biological systems and more information on the response of living organisms to the presence of nanoparticles of varying size, shape, chemical composition and surface characteristics is needed to understand and categorize the toxicity of nanoparticles. More...
6.2 Which characteristics of nanoparticles are relevant for health effects?
Studies specifically dealing with the toxicity of nanoparticles have only appeared recently and are still scarce. Most of the information available comes from studies on inhaled nanoparticles and from pharmaceutical studies in which nanomaterials are used, among other things to improve drug delivery.
The characteristics of nanoparticles that are relevant for health effects are:
- Size – In addition to being able to cross cell membranes, reach the blood and various organs because of their very small size, nanoparticles of any material have a much greater surface to volume ratio (i.e. the surface area compared to the volume) than larger particles of that same material. Therefore, relatively more molecules of the chemical are present on the surface. This may be one of the reasons why nanoparticles are generally more toxic than larger particles of the same composition.
- Chemical composition and surface characteristics – The toxicity of nanoparticles depends on their chemical composition, but also on the composition of any chemicals adsorbed onto their surfaces. However, the surfaces of nanoparticles can be modified to make them less harmful to health.
- Shape – Although there is little definitive evidence, the health effects of nanoparticles are likely to depend also on their shape. A significant example is nanotubes, which may be of a few nanometres in diameter but with a length that could be several micrometres. A recent study showed a high toxicity of carbon nanotubes which seemed to produce harmful effects by an entirely new mechanism, different from the normal model of toxic dusts.
6.3 How can inhaled nanoparticles affect health?
Particulate matter present in air pollution, especially from traffic emissions, is known to affect human health, although it is not clear exactly how. Epidemiological studies on ambient air pollution have not proved conclusively that nanoparticles are more harmful than larger particles, but these studies may not be well suited to demonstrate such differences.
Inhaled particulate matter can be deposited throughout the human respiratory tract, and an important fraction of inhaled nanoparticles deposit in the lungs. Nanoparticles can potentially move from the lungs to other organs such as the brain, the liver, the spleen and possibly the foetus in pregnant women. Data on these pathways is extremely limited but the actual number of particles that move from one organ to another can be considerable, depending on exposure time. Even within the nanoscale, size is important and small nanoparticles have been shown to be more able to reach secondary organs than larger ones.
Another potential route of inhaled nanoparticles within the body is the olfactory nerve; nanoparticles may cross the mucous membrane inside the nose and then reach the brain through the olfactory nerve. Out of three human studies, only one showed a passage of inhaled nanoparticles into the bloodstream.
Materials which by themselves are not very harmful could be toxic if they are inhaled in the form of nanoparticles.
The effects of inhaled nanoparticles in the body may include lung inflammation and heart problems. Studies in humans show that breathing in diesel soot causes a general inflammatory response and alters the system that regulates the involuntary functions in the cardiovascular system, such as control of heart rate.
The pulmonary injury and inflammation resulting from the inhalation of nanosize urban particulate matter appears to be due to the oxidative stress that these particles cause in the cells. More...
6.4 What are the health implications of nanoparticles used as drug carriers?
Nanoparticles can be used for drug delivery purposes, either as the drug itself or as the drug carrier. The product can be administered orally, applied onto the skin, or injected.
The objective of drug delivery with nanoparticles is either to get more of the drug to the target cells or to reduce the harmful effects of the free drug on other organs, or both. Nanoparticles used in this way have to circulate long distances evading the protection mechanisms of the body. To achieve this, nanoparticles are conceived to stick to cell membranes, get inside specific cells in the body or in tumours, and pass through cells. The surfaces of nanoparticles are sometimes also modified to avoid being recognized and eliminated by the immune system.
With dermal administration, it was found that particle size was less important than the total charge in terms of permeation through the skin. For instance, only negatively charged particles were found to overcome the skin barrier and only when concentration of charge was high enough.
Nanoparticles may be used effectively to deliver genes to cells, to treat cancer, as well as in vaccination .
The use of nanoparticles as drug carriers may reduce the toxicity of the incorporated drug but it is sometimes difficult to distinguish the toxicity of the drug from that of the nanoparticle. Toxicity of gold nanoparticles, for instance, has been shown at high concentrations. In addition, nanoparticles trapped in the liver can affect the function of this organ.
Nanoparticles have the potential to cross the blood brain barrier, which makes them extremely useful as a way to deliver drugs directly to the brain. On the other hand, this is also a major drawback because nanoparticles used to carry drugs may be toxic to the brain. More...
6.5 How should harmful effects of nanoparticles be assessed?
Traditionally, doses are measured in terms of mass because the harmful effects of any substance depend on the mass of the substance to which the individual is exposed. However, for nanoparticles it is more reasonable to measure doses also in terms of number of particles and their surface area because these parameters further determine the interactions of nanoparticles with biological systems.
Several hypotheses were proposed for the adverse health effects of nanoparticles as part of ambient air pollution. These hypotheses address nanoparticle characteristics, their distribution, and their effects on organ systems, including effects on immune and inflammatory systems.
However, some of these hypotheses may be of limited or no relevance for engineered nanoparticles. For instance, the adhesion of toxic substances onto the surface of nanoparticles may be of less relevance for production and handling facilities of large volumes of engineered nanoparticles compared to the particles in ambient air.
In addition, drawing conclusions from tests on healthy animal models may be unsuitable as some of the effects of nanoparticles may only be a risk for susceptible organisms and predisposed individuals, but not to healthy people. For instance, age, respiratory tract problems and other pollutants can modify the pulmonary inflammation and oxidative stress induced by nanoparticles.
Because of the specific characteristics of nanoparticles, conventional toxicity tests may not be enough to detect all their possible harmful effects. Therefore, a series of specific tests was proposed to assess the toxicity of nanoparticles used in drug delivery systems. One mechanism of toxicity of nanoparticles is likely to be the induction of oxidative stress in cells and organs. Testing for interaction of nanoparticles with proteins and various cell types should be considered as part of the toxicological evaluation.
With the exception of airborne particles delivered to the lung, information on the behaviour of nanoparticles in the body including distribution, accumulation, metabolism, and organ specific toxicity is still minimal. More...
6.6 What are the effects of nanoparticles on the environment?
There are almost no publications on the effects of engineered nanoparticles on animals and plants in the environment.
However, a number studies have examined the uptake and effects of nanoparticles at a cellular level to evaluate their impact on humans; it can reasonably be assumed that the conclusions of these studies may be extrapolated to other species, but more research is needed to confirm this assumption. Moreover, careful examination and interpretation of existing data and careful planning of new research is required to establish the true impact of nanoparticles on the environment, and the differences with larger, conventional forms of the substances.
Persistent insoluble nanoparticles may cause problems in the environment that are much greater than those revealed by human health assessments. More...