This review is written with the goal of informing public health concerns related to nanoscience, while raising awareness of nanomaterials toxicity among scientists and manufacturers handling them. We show that humans have always been exposed to nanoparticles and dust from natural sources and human activities, the recent development of industry and combustion-based engine transportation profoundly increasing anthropogenic nanoparticulate pollution. The key to understanding the toxicity of nanoparticles is that their minute size, smaller than cells and cellular organelles, allows them to penetrate these basic biological structures, disrupting their normal function. Among diseases associated with nanoparticles are asthma, bronchitis, lung cancer, neurodegenerative diseases (such as Parkinson`s and Alzheimer`s diseases), Crohn`s disease, colon cancer. Nanoparticles that enter the circulatory system are related to occurrence of arteriosclerosis, and blood clots, arrhythmia, heart diseases, and ultimately cardiac death. We show that possible adverse effects of nanoparticles on human health depend on individual factors such as genetics and existing disease, as well as exposure, and nanoparticle chemistry, size, shape, and agglomeration state. The faster we will understand their causes and mechanisms, the more likely we are to find cures for diseases associated with nanoparticle exposure. We foresee a future with better-informed, and hopefully more cautious manipulation of engineered nanomaterials, as well as the development of laws and policies for safely managing all aspects of nanomaterial manufacturing, industrial and commercial use, and recycling.

Nanomaterials and nanoparticles: Sources and toxicity

This review is presented as a common foundation for scientists interested in nanoparticles, their origin, activity, and biological toxicity. It is written with the goal of rationalizing and informing public health concerns related to this sometimes-strange new science of “nano,” while raising awareness of nanomaterials’ toxicity among scientists and manufacturers handling them. We show that humans have always been exposed to tiny particles via dust storms, volcanic ash, and other natural processes, and that our bodily systems are well adapted to protect us from these potentially harmful intruders. The reticuloendothelial system, in particular, actively neutralizes and eliminates foreign matter in the body, including viruses and nonbiological particles. Particles originating from human activities have existed for millennia, e.g., smoke from combustion and lint from garments, but the recent development of industry and combustion-based engine transportation has profoundly increased anthropogenic particulate pollution. Significantly, technological advancement has also changed the character of particulate pollution, increasing the proportion of nanometer-sized particles-“nanoparticles”-and expanding the variety of chemical compositions. Recent epidemiological studies have shown a strong correlation between particulate air pollution levels, respiratory and cardiovascular diseases, various cancers, and mortality. Adverse effects of nanoparticles on human health depend on individual factors such as genetics and existing disease, as well as exposure, and nanoparticle chemistry, size, shape, agglomeration state, and electromagnetic properties. Animal and human studies show that inhaled nanoparticles are less efficiently removed than larger particles by the macrophage clearance mechanisms in the lungs, causing lung damage, and that nanoparticles can translocate through the circulatory, lymphatic, and nervous systems to many tissues and organs, including the brain. The key to understanding the toxicity of nanoparticles is that their minute size, smaller than cells and cellular organelles, allows them to penetrate these basic biological structures, disrupting their normal function. Examples of toxic effects include tissue inflammation, and altered cellular redox balance toward oxidation, causing abnormal function or cell death. The manipulation of matter at the scale of atoms, “nanotechnology,” is creating many new materials with characteristics not always easily predicted from current knowledge. Within the nearly limitless diversity of these materials, some happen to be toxic to biological systems, others are relatively benign, while others confer health benefits. Some of these materials have desirable characteristics for industrial applications, as nanostructured materials often exhibit beneficial properties, from UV absorbance in sunscreen to oil-less lubrication of motors. A rational science-based approach is needed to minimize harm caused by these materials, while supporting continued study and appropriate industrial development. As current knowledge of the toxicology of “bulk” materials may not suffice in reliably predicting toxic forms of nanoparticles, ongoing and expanded study of “nanotoxicity” will be necessary. For nanotechnologies with clearly associated health risks, intelligent design of materials and devices is needed to derive the benefits of these new technologies while limiting adverse health impacts. Human exposure to toxic nanoparticles can be reduced through identifying creation-exposure pathways of toxins, a study that may someday soon unravel the mysteries of diseases such as Parkinson’s and Alzheimer’s. Reduction in fossil fuel combustion would have a large impact on global human exposure to nanoparticles, as would limiting deforestation and desertification. While nanotoxicity is a relatively new concept to science, this review reveals the result of life’s long history of evolution in the presence of nanoparticles, and how the human body, in particular, has adapted to defend itself against nanoparticulate intruders.

https://avs.scitation.org/doi/pdf/10.1116/1.2815690

Glomerular podocytes are highly specialized cells with a complex cytoarchitecture. Their most prominent features are interdigitated foot processes with filtration slits in between. These are bridged by the slit diaphragm, which plays a major role in establishing the selective permeability of the glomerular filtration barrier. Injury to podocytes leads to proteinuria, a hallmark of most glomerular diseases. New technical approaches have led to a considerable increase in our understanding of podocyte biology including protein inventory, composition and arrangement of the cytoskeleton, receptor equipment, and signaling pathways involved in the control of ultrafiltration. Moreover, disturbances of podocyte architecture resulting in the retraction of foot processes and proteinuria appear to be a common theme in the progression of acquired glomerular disease. In hereditary nephrotic syndromes identified over the last 2 years, all mutated gene products were localized in podocytes. This review integrates our recent physiological and molecular understanding of the role of podocytes during the maintenance and failure of the glomerular filtration barrier.

Cell Biology of the Glomerular Podocyte

Human skin is repeatedly exposed to UVR that influences the function and survival of many cell types and is regarded as the main causative factor in the induction of skin cancer. It has been traditionally believed that skin pigmentation is the most important photoprotective factor, as melanin, besides functioning as a broadband UV absorbent, has antioxidant and radical scavenging properties. Besides, many epidemiological studies have shown a lower incidence for skin cancer in individuals with darker skin compared to those with fair skin. Skin pigmentation is of great cultural and cosmetic importance, yet the role of melanin in photoprotection is still controversial. This article outlines the major acute and chronic effects of UVR on human skin, the properties of melanin, the regulation of pigmentation and its effect on skin cancer prevention.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1751-1097.2007.00226.x

The Protective Role of Melanin Against UV Damage in Human Skin

During the last few years, research on toxicologically relevant properties of engineered nanoparticles has increased tremendously. A number of international research projects and additional activities are ongoing in the EU and the US, nourishing the expectation that more relevant technical and toxicological data will be published. Their widespread use allows for potential exposure to engineered nanoparticles during the whole lifecycle of a variety of products. When looking at possible exposure routes for manufactured Nanoparticles, inhalation, dermal and oral exposure are the most obvious, depending on the type of product in which Nanoparticles are used. This review shows that (1) Nanoparticles can deposit in the respiratory tract after inhalation. For a number of nanoparticles, oxidative stress-related inflammatory reactions have been observed. Tumour-related effects have only been observed in rats, and might be related to overload conditions. There are also a few reports that indicate uptake of nanoparticles in the brain via the olfactory epithelium. Nanoparticle translocation into the systemic circulation may occur after inhalation but conflicting evidence is present on the extent of translocation. These findings urge the need for additional studies to further elucidate these findings and to characterize the physiological impact. (2) There is currently little evidence from skin penetration studies that dermal applications of metal oxide nanoparticles used in sunscreens lead to systemic exposure. However, the question has been raised whether the usual testing with healthy, intact skin will be sufficient. (3) Uptake of nanoparticles in the gastrointestinal tract after oral uptake is a known phenomenon, of which use is intentionally made in the design of food and pharmacological components. Finally, this review indicates that only few specific nanoparticles have been investigated in a limited number of test systems and extrapolation of this data to other materials is not possible. Air pollution studies have generated indirect evidence for the role of combustion derived nanoparticles (CDNP) in driving adverse health effects in susceptible groups. Experimental studies with some bulk nanoparticles (carbon black, titanium dioxide, iron oxides) that have been used for decades suggest various adverse effects. However, engineered nanomaterials with new chemical and physical properties are being produced constantly and the toxicity of these is unknown. Therefore, despite the existing database on nanoparticles, no blanket statements about human toxicity can be given at this time. In addition, limited ecotoxicological data for nanomaterials precludes a systematic assessment of the impact of Nanoparticles on ecosystems.

/pdf/the-potential-risks-of-nanomaterials-a-review-carried-out-t45f9crq14.pdf

The potential risks of nanomaterials: a review carried out for ECETOC

https://www.jidonline.org/article/S0022-202X(15)30629-1/pdf

Variations of Hair Follicle Size and Distribution in Different Body Sites

40 nm, but not 750 or 1,500 nm, Nanoparticles Enter Epidermal CD1a+ Cells after Transcutaneous Application on Human Skin

Penetration Profile of Microspheres in Follicular Targeting of Terminal Hair Follicles

Benefit and risk of organic ultraviolet filters.

The penetration of topically applied compounds varies considerably in the different regions of the human body. The presence of hair follicles significantly contributes to this effect by an increase in surface area and a disruption of the epidermal barrier towards the lower parts of the hair follicle. The human hair follicle, hereby, serves not only as a reservoir, but also as a major entry point for topically applied compounds. Topical delivery of active compounds to specific targets within the skin may help reduce side-effects caused by unspecific reactions, and may help develop new strategies in the prevention and treatment of skin diseases. Various drug carrier and drug delivery systems are currently being investigated. The aim of these investigational efforts is to direct topically applied compounds to the different types of hair follicles and, ideally, to specific compartments and cell populations within the hair follicles. Follicular targeting offers opportunities for new developments, not only in hair therapy and in the treatment of hair follicle associated diseases but also in gene therapy and immunotherapy.

Hans Schaefer

Papers

Variations of Hair Follicle Size and Distribution in Different Body Sites

40 nm, but not 750 or 1,500 nm, Nanoparticles Enter Epidermal CD1a+ Cells after Transcutaneous Application on Human Skin

Penetration Profile of Microspheres in Follicular Targeting of Terminal Hair Follicles

Benefit and risk of organic ultraviolet filters.

Follicular Targeting–A Promising Tool in Selective Dermatotherapy