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Editor's Choice

The Future of Nanotechnology in Dermatology

a report by

Adnan Nasir, MD

Clinical Assistant Professor of Dermatology, University of North Carolina Chapel Hill

Nanotechnology is the study of particles 100 nanometers (nm) in size or smaller.1 It is a relatively new discipline whose origins can be traced back to the 1950s, when Nobel prize winner and physicist Richard Feynmann proposed the idea of manufacturing devices on an atomic scale.2 As matter is reduced to the nanometer size scale, it acquires unique properties that differentiate it from its macroscopic counterparts.3 These unique properties allow for the creation of whole new families of substances and materials, which confer previously unimagined benefits to consumers and patients. While considered theoretical and impractical at the time of its conception, nanotechnology is no longer the stuff of science fiction, and products utilizing the technology continue to be developed at a prodigious rate. This article discusses the potential windfalls and pitfalls of nanotechnology in dermatology. Background There is a great deal of excitement surrounding nanotechnology in industry, science, and medicine.1,4­6 Items incorporating nanotechnology have already been manufactured in a wide variety of fields. Industrial products include automobile parts, military-grade armor, ship hull paints, filters, and ceramics. Scientific products include field devices for biodefense, microfluidic analysis columns, and nanocomputers. Medical products include nanodiagnostics, radiological imaging dyes, smart drugs, and antibacterial prosthetic implants. Consumer products range from smart appliances, glass, and paint to stain- and odor-resistant clothing. Tennis balls, bicycles, and streamlined compression body swimsuits all incorporate nanotechnology. One of the fastest growing subsets of nanotechnology is the cosmetics industry.7 A cosmetics company in the US ranks sixth among patent holders in nanotechnology. Skincare, sunscreen, shampoos, toothpastes, make-up, and nail-care products all utilize nanotechnology. What Makes Nanotechnology Special? Matter behaves differently at the nanoscale.2,4­10 This behavior can be divided into several behavior categories: chemical, optical, and physical. At the nanoscale, chemical forces work differently. For example, as particles decrease in size, their surface­volume ratio increases exponentially. This allows for the exposure of a large number of surfacereactive groups on each individual particle. The behavior of the particle will vary if the reactive groups are hydrophilic, hydrophobic, or charged. Even very weak forces, such as van der Waals forces, take on tremendous significance at the nanoscale. For example, the surface tension of polar water is strong enough to support the weight of some insects. The latter could not walk on water without a nanoengineered superhydrophobic surface on their footpads.

The interaction of small-scale particles with light also varies at the nanoscale. For example, particles that are smaller than the wavelength of ambient light may actually become invisible. Particles that interact with light of different wavelengths may appear to have different colors; therefore, a particle with no intrinsic color or dye of its own may acquire color at different sizes, as can be seen when a clear soap bubble acquires a rainbow of colors as its thickness varies with gravity. Similarly, particles can be manufactured to desired sizes to interact with specified light wavelengths, such as laser, ultraviolet (UV), or infrared. This interaction can be exploited for diagnostic and therapeutic purposes, or for energy delivery. Matter also behaves differently at the physical scale when it is smaller. At the nanoscale, gas behaves like a rainstorm, and liquid like gravel. On the nanoscale, diamonds have the hardness of cheese, and steel has the springiness and flexibility of rubber. Machines made at the nanolevel have parts that can spin faster, turn over more quickly, and operate with higher efficiency. This is what allows bacterial flagellar rotors to spin at thousands of revolutions per minute (rpm) in a nearly frictionless housing with minimal energy waste. Mixing and matching different physical, chemical, and optical properties at the nanoscale allows for the creation of a near inifinite variety of useful compounds. Currently, this process is very expensive, technology-intensive, and limited to a few large corporations, institutions, or governments. A new nanotool is being invented in each company, one discovery at a time. However, costs are dropping rapidly, and entry into the nanotechnology marketplace is picking up pace. Just as the computer revolution went from punch cards and binary machine codes to thumbnail gigahertz microprocessors and open operating systems, nanomanufacture will burgeon rapidly.2,3,6 Once the necessary components are standardized and made interoperable, nanotechnology will reach an inflection point and take off rapidly. In fact, we are almost there.

Adnan Nasir, MD, is a Clinical Assistant Professor of Dermatology at University of North Carolina (UNC) Chapel Hill, and has a special interest in inflammatory skin disease, including contact dermatitis, atopic dermatitis, and psoriasis. He is interested in the application of nanotechnology in the diagnosis and management of these conditions and in nanotoxicology. E: [email protected]

© TOUCH BRIEFINGS 2008

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Editor's Choice

What Is Possible with Nanotechnology? Nanotechnology is not only about size, but also about manufacture, design, precision, and specificity. It is not enough to have a 10nm particle; the particle must be made to pre-programmed specifications. It must be a certain length and width, and must have certain surface moieties. It must be able to interact

Nanotechnology is not only about size, but also about manufacture, design, precision, and specificity.

whiskers that are one-thousandth the size of cotton fibers. When the cotton strands are coated, liquids are unable to penetrate the fibers and subsequently roll off the surface without a trace. This is a physical, not chemical, property of the whiskers and can be incorporated into a variety of fabrics, regardless of color or composition. It also does not alter the feel, breathability, or comfort of the fabric. Furthermore, since this property is physically incorporated into the individually woven strands of the fabrics, it is a permanent feature of the fabric. It cannot be washed or diminished over time. This type of material is already available in clothing stores and catalogues for adult and children's clothing, and has also been incorporated into the fabrics of uniforms. Coated medical scrubs and white coats are already available. Silver has antibacterial properties, and in the nanometer size range is a potent antibacterial and antifungal agent. It is one of the few surface nano-sized agents known to be effective against Staphylococcus and methicillin-resistant Staphylococcus aureus (MRSA). Nano-sized silver is available as a coating that impregnates clothing11 and socks, and can even be found on the surface of children's toys. Silver in clothing can retain its potency in some products for up to 100 wash cycles. Sprays are available that incorporate nanocrystalline silver and deliver ions to a desired target. Luxury clothing purveyors advertise silver-impregnated high-quality fabrics in undergarments. The manufacturers tout the release of silver ions, particularly in areas that sweat (the inguinal folds, the axillary folds), with the idea of maintaining fresh and odor-free undergarments. The leached silver reportedly kills bacteria on contact. At the same time, some silver is permanently attached to the fabric, giving a lifetime of effectiveness. Furthermore, silver-impregnated clothing that kills bacteria and eliminates the need for bleach and for heating water in the laundry cycle, which is environmentally friendly and energy-saving. Cosmetics Sunscreen incorporating nano-sized materials has several useful properties.1,4,6,7 Normal mineral sunscreens with titanium, zinc, or iron have a greasy feel because the macroparticles require a relatively greasy vehicle for suspension and dispersion. This property is eliminated in nano-sized particulate sunscreens because the small particles spread and disperse easily in aqueous and more cosmetically elegant vehicles. Larger particles of sunscreen reflect ambient light and have an opaque appearance that wearers find unacceptable. Nano-sized particles are much smaller than the wavelength of visible light (in the

with its neighbors in a precise way. Furthermore, it must be incorporated into a larger array in a pre-determined fashion, it must lack impurities, and its manufacture must be controllable and reproducible. Automobile manufacture is the same. Individual automobile parts, from bolts and screws to dashboard electronics, are reproducibly made to high tolerances. Subsequently, they are assembled, whether by humans or machines, in an extremely precise manner. Similarly, the individual components of a drug-delivery vehicle or a nano-sized battery must be synthesized with atomic precision and then assembled in a regulated reproducible fashion. Furthermore, the process needs to be performed in high enough volume and at low enough cost to be practical. An automobile prototype may be exorbitantly expensive, but its mass-produced version needs to be affordable. Similarly, a prototype nanomaterial may require the resources and research and development efforts of a government to produce, but its mass-produced progeny should be much cheaper. The range of products incorporating nanotechnology in dermatology already exceeds the space limitations of this article. As a result, I will include only a few examples of current and potential applications of nanotechnology in dermatology. This will necessitate the omission of large families of consumer, medical, and scientific applications. Interested readers may contact the author or refer to the reference section for further reading. Consumer Goods A number of consumer items that incorporate nanotechnology have been created. One example is the racing swimsuit, most recently seen in the Beijing Olympics, which used precisely designed stretchable woven fabrics. They are made of a nylon microfiber woven with elastane and patterned like shark skin. The fabric is lightweight and dries quickly. It has 2D stretching properties and compresses the swimmer's body at specific locations to maximize hydrodynamic streamlining. Nanocomposite fibers are required so that they can be woven to the necessary high density and tensile strength for the degree of compression required. Furthermore, the fabric surface is modified to be water-repellant. The surface is cold plasma nanocoated to make it hydrophobic. The fabric absorbs only 2% of its weight in water. Predecessors absorbed as much as 50% of their weight in water. The result is a strong, lightweight, water-repellant, shark-skin-like compression bodysuit that gives swimmers a lower drag coefficient in the water and faster swim times. Another example is stain-resistant clothing. Fabrics containing nano-whiskers are stain- and liquid-repellant. One coating of fabric incorporates bristles or

Given their infinitesimal size, nanoparticles in sunscreen can be evenly coated onto the skin and therefore offer more effective protection and fewer gaps in coverage over skin contours and surface irregularities.

400­700nm range) and vanish when evenly applied on the skin. As physical blockers, metal sunscreens are more likely to protect the skin from UVA and UVB exposure. Given their infinitesimal size, nanoparticles in sunscreen can also be more evenly coated onto the skin and therefore offer more effective protection and fewer gaps in coverage over skin contours and surface

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The Future of Nanotechnology in Dermatology

irregularities. Recently, there has been concern about contact dermatitis as well as the carcinogenic properties of sunscreens containing `chemical ingredients' such as avobenzone. The so-called `mineral' sunscreens containing titanium, zinc, and iron have been offered as alternatives. Due to these advantages, a large group of manufacturers has worked to offer sunscreens containing these nano-sized metals as active ingredients. Color Control Human skin is largely translucent. Three aspects of skin beauty are color correction, gloss correction, and face-shape correction. Color comes from a combination of skin type and ambient light impinging on the skin. Only about 5% of surface light is reflected; the remainder penetrates the skin, where it is scattered and absorbed. Melanin and hemoglobin absorb almost half of the light, and the other half eventually makes its way out of the skin. Melanin absorbs UV light, hemoglobin absorbs mid-wavelength yellow and green light, and the exiting light is red or infrared. The pattern of this light gives the skin its appearance and beauty. Nanometer-thick titanium-coating mica powders can alter this pattern. If their thickness is varied, an optical phase difference can be generated. If foundation containing titanium is 130nm thick, a blue interference light is reflected. At a thickness of 150nm, the light is green. At 100nm, the light is reddish. Titanium-coated mica powders in foundation are superb at color correction, but give the skin too much gloss. When incorporated with composites of nanoscale barium chloride and sodium sulfate, this gloss gives way to a matte-like finish. If the surface coatings are larger (1,000­1,500nm), they scatter light. If 20­50% of the nano-sized titanium mica are coated in this way, they reflect light in the mid-face and scatter light on the periphery of the face. This causes facial contrast, making the face look more 3D and causing face-shape correction. These scattering properties can be modified by altering the shape of the particles themselves from plate-like to spherical to needle-like. Further modifications may be able to enhance internal reflection of light at the skin­air interface or alter the wavelength of outgoing light to create a glow. This could be used for color correction or for apparent surface correction of fine lines, blemishes, or shadows. Furthermore, variation of the size of particles is being used to create make-up colors of nearly infinite as well as iridescent hues, such as those on the wings of a butterfly. Smart Surfaces Currently available smart surfaces are self-cleaning.6 Refrigerators have been made with interiors coated to be effective at self-sterilization and deodorization. They also have antibacterial properties that allow food to stay fresher for longer, and save energy by this means. They also are lined with nano-based insulation materials that reduce energy consumption. Dishwashers have been made that wash and sterilize dishes and do so at lower temperatures. Vanadium-oxide-coated glass is a potent oxidizer under UV light. This material can be coated in hydrophobic whiskers on the surface of glass, making it hydrophobic as well. As a result, dirt, debris, and organic material are easily oxidized in sunlight and washed off in rain, making for a self-cleaning window. Medical Applications Coated Instruments Medical instruments coated with nano-silver have been shown to be antibacterial and bactericidal, able to kill even multidrug-resistant organisms.4,6 Similar effects have been shown on coated stents and coated

metal prostheses such as hip prostheses. Currently, there is a dramatic rise in colonization and infection from multidrug-resistant organisms in community and hospital settings. Furthermore, with an aging population, there is an increasing need for cardiac and orthopaedic procedures, not to

Helpful in the treatment of atopic dermatitis would be a cream that would either deliver filaggrin itself to the skin or stimulate the synthesis of filaggrin.

mention dermatological procedures. In addition, there is a growing reluctance from Medicare and other third-party payers to pay for medical complications such as infection. These facts are likely only to increase the need for these types of prostheses and instruments in the future. Vaccines Topical vaccine delivery is another future aspect of nanotechnology that has promise.12 Liposomes are spheres of lipid that contain an aqueous core. These differ from micelles in that they have a bilayer membrane. Liposomes can carry both lipid- and water-soluble components. The lipid soluble components of liposomes are in the membrane bilayer component and the water-soluble components are in the aqueous phases contained within a liposome. Multilaminar liposomes can carry larger payloads and can contain a combination of ingredients. Small liposomes are 100nm or less. Multilaminar liposomes can reach 500nm in size. The phospholipid membranes of liposomes are made of materials that are compatible with cell walls and can be designed for uptake. Vaccines made of pseudoviral nanoliposomes and micelles containing plasmid DNA have been shown to reach epidermal dendritic cell precursors such as Langerhans cells. Langerhans cells then drain to regional lymph nodes, present antigen to T cells, and elicit a potent cell-mediated immune response. This may be an effective strategy for vaccines against cutaneous and systemic infectious and neoplastic diseases. Atopic Dermatitis Typically, atopic dermatitis has been treated as an immune disorder with either topical steroids, topical immunomodulators, and systemic immunosuppression or UV light. It is becoming increasingly clear that the filaggrin gene (FLG) is critical to the development of atopic eczema and ichthyosis vulgaris. Risk associations with allergic rhinitis and asthma have also been shown. In Caucasians, mutations R501X and 2284deI4 are present in at least 7­10% of the population. Improved barrier creams are being developed using nanotechnology. One of the most helpful would be a cream that would either deliver filaggrin itself to the skin or stimulate the synthesis of filaggrin. Furthermore, the cream could be formulated to deliver filaggrin to regions where transepidermal water loss is highest. Penetration of the cornified envelope would likely require nanoliposomes.13 Lamellar Ichthyosis Traupe et al. are working on a therapy for lamellar ichthyosis.14 The defect for one variant has been localized to transglutaminase. Other genetic diseases, such as Fabry's disease, have benefited from enzyme-replacement therapy.

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Editor's Choice

Traupe's group has isolated and purified transglutaminase-1 and tagged it with six histidines for purification. They plan to package recombinant transglutaminase in cationic liposomes and make a cream for therapy. The enzyme must be stable in the cream and be taken up by keratinocytes and still maintain its activity. Liposomal packing of recombinant transglutaminase-1 as

Biopolymers incorporating nanomaterials are being incorporated into woven fabrics to make a new generation of bioactive wound dressings designed to heal wounds faster, reduce inflammation and infection, and reduce scarring.

an essential step toward enzyme-replacement therapy of transglutaminase-1deficient lamellar ichthyosis. The project is supported by a Foundation for Ichthyosis and Related Skin Types grant. If successful, enzyme-replacement therapies may be modified for other cutaneous genetic diseases. Lymph-node Mapping Sentinel lymph-node mapping is now a mainstay for surgery of intermediate-thickness and thick melanomas. It may soon be used for other types of invasive skin cancer such as squamous cell carcinoma. Currently, a colored or radioactive dye is used to determine the location of the sentinel lymph-node basin. The learning curve for this procedure is steep, and requires exposure to radioactivity. Furthermore, the dye is obscured and difficult to localize during procedures where bleeding is a problem. Tracers required for sentinel-node mapping must be optimized for hydrodynamic diameter, surface, charge, and contrast. Diameters less than 10nm can overshoot the draining lymph node. This results in the sentinel node being missed and multiple downstream nodes and possibly nodal basins being labeled. Molecules that are larger (50­100nm) either do not enter lymphatics or travel so slowly that 24 hours or more may be required for label uptake. Molecules with a negative surface charge enter lymphatics more readily and are retained in the lymph nodes better. Recently, quantum dots have proved useful in identifying sentinel nodes using infrared fluorescence.15 Quantum dots are fluorescent semiconductor nanocrystals made of a CdTe core and a CdSe shell. They are coated in an anionic oligomeric phosphine envelope. The CdTe/CdSe quantum dots are easily visible in near-infrared light (NIR). They provide excellent signal-tonoise in this range and allow for excellent realtime visualization of dye travel during a sentinel-node-mapping procedure. They also move rapidly due to their specific size of 15­20nm and are firmly anchored to lymph nodes with their anionic surface charge. Furthermore, they allow for nonradioactive detection. Once optimized, they may prove superior to other tracers for sentinel-node mapping. Wound Care Organisms such as geckos, spiders, and frogs exploit the mechanical advantages of nano-engineered materials to climb walls and stick to slick

surfaces. The feet of geckos, for example, are highly convoluted, like the villi lining the small intestine. These finger-like projections vastly increase the surface area of contact of gecko feet with any surface. This increased surface contact generates subatomic partial dipoles of electrical attraction, commonly known as van der Waals attraction. Normally, the magnitude of this force is quite small and fleeting, as electron shells rearrange themselves during contact. However, in the gecko, spiders, and certain frogs, the surface area of interaction is so enormous that the contact is strong enough to support the animal's bodyweight. Researchers at Massachusetts Institute of Technology (MIT) have created an artificial adhesive that mimics these principles.10 They have been successfully able to create a waterproof adhesive bandage, which may be a useful suture substitute. It is also biodegradable. Gecko-based adhesives have been around since 2001, but the latest version, called biorubber, uses a micropatterning technology similar to that used to make computer chips. The biorubber is then coated with a thin sugar-based glue to create a very strong adhesive. In animal models, this elicits a mild inflammatory reaction. The adhesive could be made with different patterns to tune its adhesivity, elasticity, and resilience depending on its medical application. It could also be coupled to medications, which could be released as the biorubber degrades. Biopolymers incorporating a variety of natural and synthetic materials as well as nanomaterials are being incorporated into woven fabrics to make a new generation of bioactive wound dressings designed to heal wounds faster, reduce inflammation and infection, and reduce scarring.16 Fibers can be specifically designed to be bacteriostatic or fungistatic, to absorb fluids, to be breathable, to be hemostatic or non-allergenic, and to incorporate growth factors or medications. They may contain natural materials such as alginate, chitin, and collagen. They may contain carbon fibers or be made of composite materials that are woven, non-woven, knitted, crocheted, braided, or pressed. They may have additives that relieve pain, reduce odor, or provide cushioning or breathability. They may provide compression that is fixed, variable, or graduated. Fibers can already be made from yarns of cotton, silk, polyester, nylon, or wool and coated with nanomaterials. These fibers, if coated with nanosilver 10nm in size and 0.4­0.9% in weight, are effective against most bacteria, fungi, and viruses. Smart Clothing One company is creating a nanotechnology-based fabric that has a conductive fiber grid incorporated within it.2,3,6 This is integrated into the shirt and is washable. When the shirt is connected to sensors that detect electrical activity

The high surface-to-volume ratio of nanomaterials can expose chemically reactive surface groups and convert inert macromaterials into highly reactive nanomaterials.

and also stretch, the shirt can be used to monitor its wearers. For example, athletes and patients can use the shirt to monitor heart rate and respiration. Other potential sensors could detect sweat rate and body temperature. This information could be relayed wirelessly to local or distant receivers. Researchers

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The Future of Nanotechnology in Dermatology

have also created nanobatteries that can generate electricity from the movement and rustling of fabric. In the future these integrated kinetically charged batteries could allow a shirt, or any item of fabric, to generate power. It is easy to imagine adapting such a fabric to monitor UV light exposure in patients who are sun-sensitive or to monitor body temperature in patients who have hypohidrotic disorders. Such a shirt could also detect excess sweat and locally release antiperspirant or detect warmth from itch and locally release anti-inflammatory medication. Scientific Applications Nanopore sequencing combines nanomachines with nanotechnology. The goal of nanopore sequencing is to develop a solid-state device that allows DNA to be sequenced accurately, rapidly, and cheaply. The concept is simple.5,8 A pore is devised with a diameter to allow penetration of a single strand of DNA. At the bottleneck of the pore, a device reads the base pairs as they cross the pore gap. The pore is typically incorporated into an insulating membrane that separates two ionic-solution-filled compartments. The nucleotide strand spools through the pore in a linear sequence. Temperature and ionic conditions maintain the denatured quality of the strand. As nucleotides enter the pore, they partially block or unblock the pore and alter its electrical properties. Solidstate pores with electrodes on opposite sides detect the voltage bias. Each nucleotide does so to a unique extent. Calculated theoretical currents and voltages are in picoamps. Researchers have already transported and unraveled DNA molecules in solid-state nanopores. Challenges to rapid sequencing include pore clogging and electrical noise. One method of keeping DNA in a linear arrray is to electrophoretically draw it through the confined volume of a gel or nanopore. It is estimated that a genome of one billion bases would require 100 nanopores working for 20 hours and require 2ng of material. An alternative sequencing method involves scanning tunneling microscopy, which uses currents of nanoamps. Scanning tunneling microscopes have been shown to scan surfaces at speeds of 104nm/second, which equals 30,000 bases/second if the microscope can be designed to follow only along the length of the DNA molecule. Currently, this approach is impractical for genome sequencing because DNA falls on surfaces in random coils and not along straight lines. However, it might be applicable for small segments of DNA. Rapid genome sequencing has beneficial potential implications for rapid diagnosis, accurate prognosis, and tailored individual-specific or disease-specific therapy. Pitfalls So far, this article has addressed only the benefits of nanotechnology. An emerging and less thoroughly explored aspect of nanotechnology is safety.

One property of nanomaterials that distinguishes them from their larger precursors is reactivity.4,11,17,18 The high surface-to-volume ratio of nanomaterials can expose chemically reactive surface groups and convert inert macromaterials into highly reactive nanomaterials. This can result in the formation of reactive oxygen species that generate free radicals and singlet oxygen. While useful in bactericidal applications, free radicals may be harmful if nanomaterials enter the skin or the circulation. Reactive oxygen species have the potential to damage DNA, RNA, and protein, and to oxidize and disrupt cell membranes. This can have short- and long-term consequences for exposed cells and tissues. Furthermore, the small size of nanomaterials makes containment difficult and allows easier spread through the body or dispersal in the environment. Some nanomaterials, such as carbon nanotubes, are virtually indestructible and could persist or become biomagnified in the food chain. Children and women of childbearing potential could be unintentionally exposed through products marketed specifically to them. Furthermore, the effects of toxicity may not be evident for years to decades after exposure, making safety studies difficult. Any introduction of nanomaterials in the dermatology setting should be preceded by a thorough and scientific analysis of safety concerns. Summary Nanotechnology has rapidly entered the consumer and dermatology marketplace and will continue to do so at an exponential pace. Devices and materials utilizing nanotechnology capitalize on the unique properties of matter on an ultra-small scale. The ability to precisely manufacture and manipulate particle size, shape, content, and surface properties allows for the creation of a nearly infinite variety of substances superior to their predecessors. The benefits of this technology have already been seen in consumer goods and skincare products and will soon be available for medical diagnosis and treatment. In parallel with nanotechnology's progress in medicine, society, and the environment, awareness of pitfalls and timely preventive measures will become equally paramount. Acknowledgments The author would like to thank Dr Anthony Gaspari for guidance and mentorship in the field of nanotechnology in dermatology and in contact dermatitis. The author would like to acknowledge Dr Lowell Goldsmith for useful advice and comments. Disclaimer The author has no conflicts of interest to declare with respect to the contents of this article.

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6. 7.

Bhushan B, Springer Handbook of Nanotechnology, 2nd ed, Knovel, 2007. Dexler KE, Machine-Phase Nanotechnology, Scientific American Magazine, September 2001; . Drexler KE, Nanosystems: molecular machinery, manufacturing, and computation, New York, NY: John Wiley & Sons, Inc., 1992. Castanedo-Tardan MP, et al., Better Understanding the Chemicals That Surround Us, Skin and Ageing, 2007;15: 7. Gracheva ME, et al., Simulation of the electric response of DNA translocation through a semiconductor nanopore­capacitor. Available at: www.stacks.iop.org/Nano/17/622 (accessed January 6, 2006). Hall JS, Nanofuture: What's Next For Nanotechnology, Amherst, New York: Prometheus Books, 2005. Katz LM, Nanotechnology and applications in cosmetics: General

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overview, A.C.S. symposium series, 2007;961:193­200. Deamer DW, Branton D, Characterization of Nucleic Acids by Nanopore Analysis, Acc Chem Res, 2002;35:817­25. Lee HJ, et al., Antibacterial effect of nanosized silver colloidal solution on textile fabrics, J Mater Sci, 2003;38:2199­2204. Mahdavi A, et al., A biodegradable and biocompatible Geckoinspired tissue adhesive, Proc Natl Acad Sci U S A, 2008;105(7): 2307­12. Nasir A, Dermatologic toxicity of nanoengineered materials, Arch Dermatol, 2008;144(2):253­4. Reddy ST, et al., Exploiting lymphatic transport and complement activation in nanoparticle vaccines, Nat Biotechnol, 2007;25: 1159­64. Vo-Dinh T, Nanotechnology in Biology and Medicine: Methods, Devices, and Applications, Boca Raton: CRC Press, 2007.

14. Schmuth M, et al., Ichthyosis Update: Towards a Function-Driven Model of Pathogenesis of the Disorders of Cornification and the Role of Corneocyte Proteins in These Disorders, Adv Dermatol, 2007;23:231­56. 15. Kim S, et al., Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping, Nat Biotechnol, 2004;22(1):93­7. 16. Petrulyte S, Advanced textile materials and biopolymers in wound management, Dan Med Bull, 2008;55:72­7. 17. Nel A, et al., Toxic potential of materials at the nanolevel, Science, 2006;311(5761):622­7. 18. Oberdorster G, et al., Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy, Particle and Fibre Toxicology, 2005;2:8.

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