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Keywords:

  • biopsy;
  • dermatology;
  • diagnosis;
  • drug delivery;
  • lotus effect;
  • nanoshells;
  • nanotechnology;
  • optics;
  • photobiology;
  • quantum dots;
  • Raman spectroscopy;
  • sentinel lymph node;
  • therapy

Abstract

  1. Top of page
  2. Abstract
  3. Background
  4. Consumer applications
  5. Diagnosis of skin disease
  6. Biosensors
  7. Therapy
  8. Summary
  9. Acknowledgements
  10. References

This review focuses on the optical properties of matter on the nanoscale and discusses some of their potential applications in dermatology. The applications will be divided into three main categories: those with consumer potential; those with diagnostic potential; and those with therapeutic potential.

Nanotechnology is the exploration of the properties of matter on an infinitesimally small size scale. The range varies from 1 to 100 nm in some classifications and from 1 to 1000 nm in others. These ranges are larger than atoms and molecules and smaller than cellular organelles and viruses. Biologically, the nanoscale is very important, because it is the size range at which most life processes occur. Substances behave differently from their bulk precursors on the nanoscale. For example, brittle insulators, like glass, are soft and flexible and conduct electricity on the nanoscale. Motors, like flagellar rotors, can spin quite rapidly and generate a great deal of power. The goal of nanotechnology is to combine the properties of small-scale matter with purposeful design to generate a useful product. For example, a carbon nanotube cylinder by itself might have interesting properties, for example, high tensile strength, conductivity, and the ability to form covalent linkages with a variety of organic and inorganic moieties. If the nanotube were made uniformly and reproducibly, but served no purpose, other than conducting electricity, it would not be an example of nanotechnology (1). However, if it were coupled to an antibody, placed across an electrical gap, and its conductivity is measured in the presence or absence of antigen, it could be used to create a biosensor smaller than an organelle. This, then would be an example of nanotechnology. A nanoliposome of a small size and small carrying capacity would not be an example of nanotechnology. If such a liposome were designed to carry hydroxychloroquine, and target its release in T cells, this type of purposeful design meets the criteria of nanotechnology. This review focuses on the optical properties of matter on the nanoscale and discusses some of their potential applications in dermatology. The applications will be divided into three main categories: those with consumer potential; those with diagnostic potential; and those with therapeutic potential.

Background

  1. Top of page
  2. Abstract
  3. Background
  4. Consumer applications
  5. Diagnosis of skin disease
  6. Biosensors
  7. Therapy
  8. Summary
  9. Acknowledgements
  10. References

As matter shrinks, its physical, mechanical, optical, and chemical properties change. As it shrinks, its physical dimensions shrink in two aspects: its volume shrinks, and its surface area increases. Its surface-to-volume ratio increases exponentially. As a result, when a particle gets smaller, its reactivity with surrounding matter increases. Furthermore, smaller particles obey scaling laws. These are physical laws that govern Newtonian physics. For example, lever arms that are smaller can spin faster and experience the same dynamic forces. These scaling laws allow nanomechanical motors such as enzymes to operate at very high speeds. If molecules are computer simulated as ball and stick models, scaling laws make diamonds rubbery hard, steel spongy soft, and glass highly flexible on the nanoscale. Liquids slosh like loads of gravel, and photons pelt like hail. The optical properties of matter also change as particles become smaller than the wavelength of light with which they interact. Depending on their size and configuration, nanoparticles may resonate with incident light, and as a result, fluoresce, or generate heat. Some chemical interactions take on greater significance. For example, van der Waals forces, which are extremely weak on the macro scale, are magnified on the nanoscale, and allow molecules to self-assemble. Nanotechnology broadly encompasses nanomaterials, nanodevices, and nanostructures (2). In dermatology, the greatest advances in nanotechnology have been in nanomaterials such as nanoparticles for drug delivery. Nanoparticles can either be organic (examples include dendrimers) or inorganic (examples include quantum dots and gold nanoshells), and they can be configured and manipulated in a variety of ways to stabilize and deliver active ingredients to target cells and tissues (3–5). They are very tiny, very precisely engineered, and very powerful.

Consumer applications

  1. Top of page
  2. Abstract
  3. Background
  4. Consumer applications
  5. Diagnosis of skin disease
  6. Biosensors
  7. Therapy
  8. Summary
  9. Acknowledgements
  10. References

Self-cleaning surfaces

Self-cleaning surfaces using nanotechnology are being developed at a rapid rate. Self-cleaning surfaces oxidize organic matter and detoxify it. Originally, oxidation was mediated by ultraviolet (UV) light. Recent advances have allowed this effect to occur in the visible spectrum (6). The purposeful design of self-cleaning surfaces on the nanoscale is based in part on the Lotus effect (7–11). The lotus is a plant that grows in stationary ponds and pools. Its waxy surface is exposed to sunlight, which allows for photosynthesis. Because the plant is immobile, dust settling on its surface can accumulate over time and block sunlight. Dust can also block plant–air gas exchange. The lotus flower overcomes this fate with a slightly slanted surface, which is superhydrophobic. A hydrophobic surface is nonpolar. A superhydrophobic surface is a nonpolar surface with a fine structure of nanopillars. These pillars, like intestinal villi, greatly increase the surface area of the plant. They create nanospikes that suspend water above the mean surface level of the plant. They greatly decrease the contact angle of water and the plant, essentially creating spherical droplets of water with near horizontal contact angles, rather than ellipsoid or ovoid droplets with near vertical contact angles. The surface is so hydrophobic that water rolls down the slant of the plant easily. It is also so hydrophobic that any material on the plant, be it dust or debris, has a greater affinity for a rolling water droplet than the plant. Thus, moisture from dew or from rain lands on the plant, rolls off, and carries with it any suffocating dust and debris, keeping the plant clean. Self-cleaning surfaces made from nanopillars of titanium dioxide and vanadium dioxide have been manufactured to high tolerances. These surfaces have the additional property of being highly oxidative in the presence of UV light. Manufacturing methods have reduced the band gap to the 3 eV range and extended the oxidation capability of these surfaces into the visible light range. Microbes – including drug-resistant microorganisms – are readily killed in the presence of UV light. Any organic materials on oxidative surfaces are coupled with oxygen, made polar, and are easily dissolved in water or a polar cleaning solution. Self-cleaning surfaces are gaining utility in the consumer marketplace in the form of fabrics, appliances, and kitchen surfaces. They are also being used in medicine for sterile rooms, equipment, and in prosthetic implants.

Sunscreens

Sunscreens are the basis of photoprotection in dermatology. Most sunscreens made with physical blockers, such as iron, titanium, and zinc, have been traditionally difficult to suspend in nongreasy vehicles. They also leave a whitish residue on the skin, which many consumers find unacceptable. The advent of nanosized sunscreen has led to several enhancements. Smaller particles of sunscreen, with their higher surface-to-volume ratio, and with the presence of polar oxygen on the surface (in the form of, for example, titanium dioxide), have increased solubility in water-based emulsions. This allows them to be suspended in greaseless vehicles. Small particles of sunscreen pack more tightly and can cover the skin more evenly. Small particles, are also more occlusive and enhance skin barrier function. Nanoparticles of sunscreen are smaller than the wavelength of visible light (400–700 nm), and are essentially invisible on application. These enhancements lead to sunscreens with better consumer acceptance, and possibly, compliance. There is a theoretic concern that nanoparticulate sunscreens may be more reactive, especially through the generation of reactive oxygen species. The studies on nanoparticulate sunscreen safety are ongoing. Some researchers report that the sunscreen nanoparticles marketed to consumers are coated to prevent oxidative damage, and that it is the uncoated nanoparticle in sunscreen which is responsible for most of the toxicity described in studies. There is also concern that nanoparticulate sunscreens may penetrate the epidermis, where they have the potential to do harm. Studies have both supported and refuted this concern (3, 12–18).

Diagnosis of skin disease

  1. Top of page
  2. Abstract
  3. Background
  4. Consumer applications
  5. Diagnosis of skin disease
  6. Biosensors
  7. Therapy
  8. Summary
  9. Acknowledgements
  10. References

Nanotechnology will fundamentally alter the way in which we diagnose disease. Devices using nanotechnology for diagnosis will be smaller, on the order of a cellular organelle, multiplexed, rapid, and highly sensitive, requiring miniscule amounts of analytic material, and highly specific. The traditional tools of diagnosis used clinically today – biopsies, tissue or fungal cultures, blood testing, and imaging techniques – will be unrecognizable. Traditional techniques, especially biopsies and blood testing, are painful. Biopsies may scar. Biopsy results may take several days, or longer, if special tests are required. Tissue cultures may be delayed by weeks. Tissue culture may be falsely negative if the specimen is sterile or not grown under ideal culture conditions. Our current diagnostic methodologies – while well established in the literature – may become superseded by new tools. Nanotechnologic tests will be more rapid, less invasive, more sensitive, and more specific than what we have today. Space limitations prevent a comprehensive discussion of all the possible diagnostic methods using nanotechnology, which are currently being studied. In this section, we will explore just two diagnostic methods, distributed optics and quantum dots, both of which are in development stages.

Optical fabrics

Distributed optics will have many applications in dermatology, both for the diagnosis and management of skin disease. Distributed optics is currently being used clinically for monitoring of respiration in wearable textiles embedded with optoelectronic fibers (19–23). Distributed optics can be used for imaging. Fink and colleagues have created a submillimeter fiber containing nested rings of 100 nm light-sensitive semiconductor materials (22, 23). The rings are encased in an insulated polymer. These fibers can be made reproducibly and woven into fabric. When an object, such as the smiley face used in Fink's study, is placed in between a light source and a patch of fabric, light illuminates the fabric in a pattern, and is converted into electricity by the semiconductor. The signal is then amplified, and collated in a computer. The pattern of electrical signals can then be converted into an image, which faithfully reproduces the smiley face. A tight-fitting optical suit could have several dermatologic applications such as mapping of moles or tracking body surface area of psoriasis or atopic dermatitis. Not only could such a suit provide dimensions of skin lesions, it might also be able to give contour information. Optical suits might also work by detecting temperature changes in the skin and mapping them on the surface for monitoring inflammatory diseases such as psoriasis, atopic dermatitis, or mycosis fungoides. The potential for ‘reversing the flow’ and creating a light delivery system might have implications for the treatment of skin disease. For example, a semiconductor laser in the narrow-band UVB range might be useful for therapeutic optical suit, by delivering light in a pattern that matches psoriasis (21). The treatment could be performed overnight as a patient sleeps in optical pajamas, or during the day in winter if the patient wears optical thermal underwear.

Quantum dots

Quantum dots are highly fluorescent molecular beacons, and their absorption and emission spectra can be tuned over a broad range of frequencies from infrared to UV. Quantum dots trace their origins in the extensive study of semiconductor systems. By confining electrons to one-, two-, and three-dimensional immobile shapes such as planes, lines, or points (24), scientists can control semiconductor geometry. Point – or one-dimensional – confinement generates the so-called ‘quantum dots’. Quantum dots are fluorescent nanoparticles of 100 Å diameter whose properties can be changed in a controlled manner through electrostatic gates, changes in dot geometry, or applied magnetic fields (24, 25). These dots were first discovered by Ekimov and Onushchenko in 1981 (26), who described them as three-dimensional microscopic crystals of semiconducting compounds grown in a transparent dielectric matrix. As they increased the average radius of the crystals, the absorption spectra showed two intense lines, but as they reduced the average radius, there was a short-wave shift and a broadening of the excitation–absorption lines due to an increase in the energy of the particles in the potential well (26). These wells are now utilized in such applications as commonplace as compact disks and television satellite receivers.

Quantum dots have been likened to synthetic atoms as they have very similar structures to natural atoms, except that they are fabricated in the laboratory, and have properties that increase their multifunctionality (25). A common way to fabricate quantum dots is to use electrostatic gate mechanisms or etching techniques to force electron gas into a desired conformation (25). This fabrication technique has led to entire surfaces in which virtually all of the properties of each individual atom can be controlled experimentally (24). Controllable surfaces are the hallmark of computing advances. Quantum dots have been freed from the plane of the silicone chip into isolated floating nanoparticles. They are now being used in the biomedical industry.

Quantum dots are intensely bright, and their fluorescence is stable, long lasting, and unquenchable. When they are covalently coupled with receptor molecules, their fluorescence shifts in the presence or absence of a cognate ligand. Ligand–receptor quantum dots have been used to label protein biomarkers for breast cancer as well as for subpicomolar quantification of proteins (27). The most common biomedical dot to be used contains a cadmium selenide core and zinc sulfide shell with a polymeric ligand-rich coating – this allows the dots to emit fluorescence based on its size and chemical composition (27). Laser light shined onto a quantum dot results in an individualized emission spectrum for the quantum dot, which varies for the medium- or ligand-coupling state of the dot. This method has been applied to tumor localization without the use of radioactive tracers or blue dyes. When tuned to the near infrared-fluorescent wavelength (800 nm), they fluoresce brightly and stably. The NIR wavelength penetrates the tissue deeply. It is nontoxic to living tissue and has been used for years in clinical applications such as pulse oximetry. There is very low autofluorescence of tissue in this wavelength range, and the signal-to-noise ratio is very high. Sentinel lymph node mapping has been successful in animal studies and has been examined in human studies for mapping and imaging lung cancer, gastric cancer, and breast cancer lymph node basins in vivo and in real time (28–36).

Tumor imaging is a field in which nanostructures have become increasingly valuable. Fluorescent nanoparticles are able to profile tumor biomarkers by antibody conjugation and detect multiple genes with in situ hybridization (27). These techniques can be used in different types of tumor identification including near-infrared narrow-band imaging for surgical resection and magnetic resonance guidance (37, 38). The most obvious advantages to these techniques are diagnosis, identification, and staging of tumors with greater speed and efficiency, and less toxicity. The sentinel node biopsy is still recommended for staging melanoma patients by the American Joint Committee on Cancer staging system (39, 78–81). Sentinel node biopsy is being enhanced with the advent of quantum dots. Topical application of quantum dots would allow for sentinel node evaluation without disturbing the skin or the tumor being evaluated (40).

Quantum dot penetration depends on the type of dot, its shape, size, and/or surface charge, the condition of the skin, as well as the shape and texture of the core and the coating. Studies indicate that the most likely path of penetration of quantum dots through the skin is via the intercellular space between corneocytes and into the bilipid layer, while they agglomerate in the stratum corneum layer and hair follicles (41, 31, 42). Dots in a more flexible vehicle are more successful than rigid vehicles in penetrating deeper layers of the skin due to their ability to penetrate irregular interstices varying in size and shape between cells (41). A polyethylene glycol coating led to more successful penetration in a study where the PEG-coated dots were able to penetrate the uppermost layers of porcine stratum corneum and the vacuoles of human epidermal keratinocytes after 24 h of exposure (41). The authors noted that if the skin was damaged, there was greater penetration at the risk of an inflammatory response (41, 31). When the skin of murine models was damaged by UV radiation, there was a higher level of penetration that extended into the dermal layer due to lipid destruction in the stratum corneum (31). In one study, ethosomes and quantum dots were fused and shown to penetrate scar tissue (43). Quantum dots have been used for selective photothermolysis, and this application may be useful for scar therapy.

When used in significant doses, quantum dots can have toxic effects on the human body due to their heavy-metal core. Formulations of biocompatible quantum dots are being developed to make the procedure less toxic. While the technology of how to create and use quantum dots in clinical applications is still very young and largely theoretical, it is growing at an exponential rate and is likely to be more significant in the years and decades to come.

Raman spectroscopy

Raman spectroscopy is a method that detects vibrations of covalent bonds between atoms in a molecule stimulated by light. The emission spectrum of each bond is unique, and the sum of spectra from multiple bonds in a complex molecule can be used to develop a spectroscopic fingerprint (44, 45). The molecule-specific peaks and widths of each of these spectra create a unique pattern, which can be used to identify that substance in an unknown sample. This method has recently gained attention due to its potential for biomedical application, as it is ideally suited for detecting small changes in trace substances in a complex biomolecular environment (45). Quantum dots and other nanoparticles can be used as Raman probes to localize and quantify multiple targets (such as nucleic acids, proteins, and small molecules) within a tumor section (27).

The sensitivity of the Raman method has been significantly improved with advances in optics and software. Raman spectroscopy is able to penetrate deep into the tissue, is extremely sensitive (to molecular structure, conformation, and chemical interactions), does not require special sample preparation, can image subcellular organelles and small tumors (46, 47), and has the potential for automation. This method can be utilized both for tissue sections and for tissue blocks due to its ability to penetrate skin deeper, and it has been proven to be able to distinguish between healthy and cancerous tissue for multiple types of carcinomas including lung, skin, breast, and others (47). Raman spectroscopy may be a suitable tool for cancer diagnosis because it can easily identify some features of malignancy such as increased nucleus : cytoplasm ratio, disordered chromatin, higher metabolic activity, and changes in lipid and protein levels (47). The most clinically applicable use for this method in dermatology may be in dermatologic surgery. In a study performed by Larraona-Puy (47), Raman spectroscopy was suggested as a method to delineate margins for each layer of excision of basal cell carcinoma in Mohs micrographic surgery. The construction of an accurate, reproducible Raman-based instrument would be a useful adjunct to this specific type of skin surgery and could potentially be modified for the visualization and removal of tumors not yet readily amenable to Mohs, such as melanoma.

Biosensors

  1. Top of page
  2. Abstract
  3. Background
  4. Consumer applications
  5. Diagnosis of skin disease
  6. Biosensors
  7. Therapy
  8. Summary
  9. Acknowledgements
  10. References

Surface plasmon resonance

Surface plasmons are defined as collective oscillations of free electrons at metallic-dielectric surfaces (typically Au, Ag, Cu, Al, Pt, etc.). At their resonant frequency, plasmons can give rise to very intense scattering of emitted light (48). When a nanostructured surface is placed against a prism, surface plasmon resonance changes the energy of reflected light. This energy change is manifested as a change in wavelength. An energy gain leads to a shorter wavelength of reflected light, and an energy loss results in a longer wavelength of the reflected light. This change in wavelength effectively results in an alteration in the prism's apparent refractive index. This index shift can then be used in a diagnostic application. Subtle changes in the properties of the surface induced, for example, by the presence of an analyte, can lead to dramatic changes in surface plasmon resonance (49, 50). The plasmon resonance effect is more efficient on nanospheres than on nanofilms. Theoretical calculations have shown an intensity enhancement of more than 500-fold for nanospheres compared with nanofilms of the same wavelength (51). The ability of plasmon resonance to detect subnanometer irregularities in surfaces has led to a multitude of applications, including detection of molecular adsorption for polymers, nucleic acids, and proteins, exploitation of photovoltaic cells to increase light absorption, the measurement of the thickness of adsorbed self-assembled nanofilms, screening for antibodies against nucleophilic amino acids, analysis of biomolecules, molecular-recognition elements and amplifiers, and detection of blood glucose in complex mixtures such as interstitial fluid, among others (1, 52–56). The assays require very little analyte, and results can be visualized in real time. Atoms, molecules, toxins, and pathogens can all be detected. For instance, Baac (57) was able to directly detect the insect pathogen baculovirus. The technique may have utility for real-time detection of medically important pathogens. Surface plasmon resonance has been used to detect herpes simplex virus and varicella zoster virus. It has been used to diagnose allergies (1, 58). Its sensitivity may be useful for biomarker analysis. Plasmon resonance can also analyze complex mixtures. A label-free localized surface plasmon resonance sensor that operates in the NIR region was able to detect low concentrations of analytes in whole blood in just a few minutes' time without sample separation or centrifugation (49). Plasmon resonance may be useful for real-time tracking of the molecular and cellular changes in the progression from prelesional to lesional skin. It has been used to track the production corneodesmosin in epidermal differentiation (59).

Surface plasmon resonance is versatile. It has immense potential for the utilization of in both a medical and laboratory setting. It is a rapid, real-time, and nonlabeling analytic technique. It is compact enough for portable applications and requires few disposable components (57).

Therapy

  1. Top of page
  2. Abstract
  3. Background
  4. Consumer applications
  5. Diagnosis of skin disease
  6. Biosensors
  7. Therapy
  8. Summary
  9. Acknowledgements
  10. References

Gold nanoshell

Gold nanoparticles have unique optical properties based on specific characteristics of their size, shape, and thickness. Bulk gold has a yellow color with a metallic shine because the electrons on its surface are shared and emit light in the yellow spectrum when going from an excited state to the ground state. On the nanoscale, constraints in shape size and surface structure of a gold nanoparticle lead to a phenomenon known as surface plasmon resonance. This is a collective oscillation or resonance of electrons on the surface of a nanoparticle. The resonant effect is extremely powerful. When stimulated by incident light in phase with the oscillations and at the same resonance frequency as the nanoparticle, the output of these oscillations can be enhanced by orders of magnitude on the surface of nanoparticles. This magnification of the effect of light has important implications for biology, particularly in the area of photothermolysis.

Gold nanoshells can be optically tuned to desired wavelengths that provide an optimum contrast between hemoglobin and the nanoshell, are inert and bioconjugatable, and have enhanced permeability and retention in tumors, all of which make them desirable structures for imaging techniques (37). In an elegant study, Lu et al. (60) generated 40 nm gold nanoshells for selective photothermolysis based on surface plasmon resonance. The nanoshells were optimized for peak resonance in the near infrared range at 808 nm. The efficiency of gold as a thermal coupling agent is remarkable. Mie scattering theory predicts that a gold nanoparticle is 1 million times as efficient in converting incident light into energy as a near infrared dye such as indocyanine green (38). Hollow gold nanoshells thus tuned were coated in polyethylene glycol to make them soluble in normal saline and to prevent aggregation. They were targeted to melanocytes by a coating of melanocyte stimulating hormone (MSH). These nanospheres are stabilized and then specifically taken up by cancer cells via receptor-mediated endocytosis (61). The authors were able to demonstrate significant heating of the gold nanoshells with an 808 nm laser at 8 W/cm2. When mice were implanted with melanoma and externally irradiated with 808 nm laser light at 32 W/cm2 for 3 min, significant shrinkage of melanoma was observed on mice injected with MSH-coated gold nanoshells. Shrunken tumors showed pyknosis, karyolysis, acidophilia, and extracellular matrix degradation. Control mice injected with saline or injected with PEG-coated (but not MSH coated) nanoshells showed no regression of tumor and no histologic damage to tumor when irradiated with laser light. While the actual temperatures generated on tumor vs. surrounding tissue was not carried out in this study, another study using gold nanoshells to treat breast cancer showed temperatures elevations to 61 °C and temperature increases of 25–30 °C up to a depth of 3 cm from the surface of the skin. Selective photothermolysis using gold nanoshells for other cutaneous tumors such as basal cell carcinoma and squamous cell carcinoma will require biomarkers for targeting. These spheres have many inherent advantages: they increase the efficiency of photoablation, decrease the energy required of the laser, minimize potential harm to surrounding tissue, and display prolonged half-life for increased targeting through leaky tumor vasculature, and their shape, size, general construction, and tunability make them prime candidates for antitumor applications (61). Because normal tissue is unharmed, nanoshell-guided selective photothermolysis may be useful for treating cutaneous tumors with ill-defined margins, up to a depth of several centimeters, as demonstrated in studies of photothermolysis of breast cancer (38).

Other applications of selective photothermolysis

Like gold nanoshells, nanotubes can be targeted to tumors, generate heat by absorbing near-infrared light waves, and then destroy surrounding cells (62). Nanobombs can destroy cancerous cells, surrounding vasculature that nourish diseased cells, and clear debris, including any nanostructure that helped to identify the margins of the tumor; however, these nanobombs can be toxic if administered in significant amounts or could damage surrounding healthy cells (62). A less toxic approach to photoablation can be performed by a combination of hyperthermia and heat shock protein 70 with nanoparticles; this technique showed complete regression of B16 melanoma in 90% of murine models in one study (63). Another experimental design, which used a pairing of a magnetite conjugate along with metallic nanoparticles, was used to selectively destroy melanoma cells by nonapoptotic cell death within 10 min (64). Interestingly, a control in this study showed that the nanoparticle injection itself in the absence of an increased temperature possessed an ‘intrinsic cytotoxicity against melanoma cells’ (64).

Drug delivery using nanoparticles

The most common application of nanotechnology in dermatology is in the construction and manipulation of nanoparticles. There is a tremendous potential for nanoparticle-driven drug delivery, which has led to a huge swell of interest in this area. The many advantages of nanovehicles include their small size, customizable surface properties, tunable solubility, and multifunctionality (2, 65–73). They pave the way for new ground to break in biomedical applications.

Nanoparticles are generally divided in into two large categories: those that contain organic molecules as their principal structural component (i.e. liposomes, dendrimers, nanotubes, etc.), and those that have a structural core or shell of inorganic elements (2, 27). These nanoparticles come in many forms each of which have their own individual advantages and disadvantages. Some of the main forms include metallic nanoshells or nanospheres, nanotubes, nanocapsules, and polymer-based nanoparticles. By changing the core and shell design of these nanoparticles – which defines characteristics such as fluorescence, optical, magnetic, and electronic properties – it is possible to develop a nearly infinite variety of applications. Nanovehicles can be used to stabilize drugs, sequester drugs, control drug release rate, and target drugs.

Metallic nanoshells and nanospheres are nanoscale structures often coated in a conductive metal, typically gold or silver. Drug is distributed on the surface or the interior of these nanoparticles. Organic nanocapsules tend to confine a drug to a polymer membrane (27). The advantages of facilitated nanodrug delivery include reduced toxicity on healthy tissues (73), increased drug stability, increased drug potency and efficacy, enhanced cell and tissue uptake, improved bioavailability, control (sustained release, burst release, rate-controlled release), optimal solubility for systemic delivery, the ability to cross the blood–brain barrier along with other biological barriers (2, 27). Characteristic properties have been associated with different types of nanocarriers. These include the use of hydrogels to stimulate the immune system, the use of micelles or liposomes to increase solubility and half-life, and the use of dendrimers to increase tumor uptake and thereby decrease toxicity. Nanotubes travel efficiently via the vasculature, and readily enter fenestrated capillaries associated with tumor neoangiogenesis.

Nanoparticle drugs are not without disadvantages and potential toxicities (3, 12, 74–76, 13–15, 77, 17, 18). Nanoparticulate drugs have a greater risk of aggregation during storage and transport. They have a greater risk of dispersion due to smaller particle size. They can have the potential to be recognized by the host immune system or cleared from circulation by the reticuloendothelial system. They are more susceptible to clumping if uncoated (27). Polymer coatings tend to minimize these drawbacks. Other techniques to reduce toxicity include purer manufacture, reduction in heavy metal contamination, reduction of oxidative potential, enhancement of biodegradation and bioelimination, minimization of bioaccumulation, and minimization of penetration into nontarget tissues.

Nanoparticles that can deliver drugs in response to a variety of stimuli are being created, including light of a particular wavelength, ultrasound, electricity, temperature, magnetism, and radiofrequency. The implications for the management of cutaneous disease are enormous.

Summary

  1. Top of page
  2. Abstract
  3. Background
  4. Consumer applications
  5. Diagnosis of skin disease
  6. Biosensors
  7. Therapy
  8. Summary
  9. Acknowledgements
  10. References

Nanotechnology is a rapidly growing discipline rooted in physics, chemistry, and engineering. An enormous number of patents have been issued in nanotechnology in the consumer and medical sectors. One of the largest areas of growth for nanotechnology in medicine has been dermatology. The skin is the first point of contact for nanomaterials and an optimum target for nanomaterials, nanodrugs, and nanodevices. Much of skin disease resides within a few centimeters of the dermis. Nanotechnology and optics are an ideal combination for exploring new tools and methods for the diagnosis and management of skin disease. Phenomena such as superhydrophobicity, quantum dot fluorescence, surface plasmon resonance, Raman effect, and responsive nanodelivery systems, which depend on light, heat, and radiofrequency for activation, are being used to create the next generation of dermatologic advances. While they are still in the very beginnings of their research and implementation phases, the benefits of the new developments are obvious: they will be more specific, more sensitive, less invasive, more compact, and faster than before. Because of space limitations, only a few of the new techniques are discussed in this review. There are many, many more in the pipeline. This is an exciting time for dermatology.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Background
  4. Consumer applications
  5. Diagnosis of skin disease
  6. Biosensors
  7. Therapy
  8. Summary
  9. Acknowledgements
  10. References

The authors would like to thank Drs. Anthony Gaspari and R. Rox Anderson for useful discussions and information regarding this manuscript. Portions of this review were presented at the Photomedicine Society meeting in Miami, FL, in March 2010.

References

  1. Top of page
  2. Abstract
  3. Background
  4. Consumer applications
  5. Diagnosis of skin disease
  6. Biosensors
  7. Therapy
  8. Summary
  9. Acknowledgements
  10. References