Recent studies have attempted to identify more precisely the most effective wavelengths for the treatment of sebaceous glands, which are directly involved in the pathophysiology of acne. With a free electron laser, which can be tuned to any wavelength on the electromagnetic spectrum, we find absorption peaks in the sebaceous glands at 1210, 1728, 1760, 2306, and 2346nm. With pulses of 100-125ms in the range of 1700nm, a free electron laser can induce selective thermal damage to sebaceous glands.

PDT has also been shown to cause some degree of inhibition of the sebaceous glands, which has a beneficial effect on inflammatory acne lesions. To avoid excessive damage to the keratinocytes, exposure to low-power red light (635nm) or blue light (420nm) has been used successfully during incubation with aminolevulinic acid (ALA), thereby preventing the massive accumulation of protoporphyrinIX. Protoporphyrin IX causes cytotoxic damage to keratinocytes on exposure to high-energy red light. The use of PDT with low-power red or blue light has been called inhibition photodynamic therapy (I-PDT).24

Among the absorption peaks for the various cutaneous lipids, the 1210nm wavelength stands out for its ability to cause selective thermal damage to subcutaneous tissue when used in combination with epidermal cooling systems. At this wavelength, a new therapeutic concept called selective photothermostimulation (SPS) occurs. SPS could have the capacity to stimulate the adipocytes and mesenchymal cells in the subcutaneous tissue, making it useful for treating cellulite and even large lipomas. Satisfactory results have also been obtained with fibers placed laterally underneath the skin surface that deliver 1440nm laser pulses to the dermal-hypodermal interface.25

Various wavelengths (Nd:YAG, 924/927nm diode, 800nm diode) have been used to destroy eccrine sweat glands in axillary hyperhidrosis. Radiofrequency and ultrasound systems have also been used to induce thermal damage in these glands. In 2011, the US Food and Drug Administration approved a microwave-based device for the treatment of axillary hyperhidrosis.26–31

Ultra-short-pulse (picosecond) lasers appear to be superior to nanosecond-pulse lasers in pigment removal, especially for colors—such as blue and green—that are resistant to removal with current systems.32–36 These devices operate on familiar wavelengths. Alexandrite and Nd:YAG lasers are used to remove black, blue, and green pigments, while 532nm Nd:YAG lasers are used to remove red, yellow, and orange pigments.

Research has shown that exposing Trichophytonrubrum to 42.5°C for 2minutes can inactivate the fungus. However, the conclusions of this in vitro study cannot be extrapolated to the conditions of clinical practice. Q-switched pulsed Nd:YAG lasers and 1320, 870, and 930nm lasers have been used in the treatment of onychomycosis.37–41 Studies of PDT have demonstrated that this technique is useful even in onychomycosis caused by nondermatophyte fungi, which tend to respond very poorly to conventional pharmacotherapies.42,43

The efficacy demonstrated in some studies by vascular laser treatment in diseases such as lupus erythematosus, psoriasis, and inflammatory rosacea may be due not only to the effect of the lasers on the vessels but also to the suspected involvement of certain immune modulation mechanisms.44,45

Recent studies have demonstrated the efficacy of vascular laser treatment against basal cell carcinoma.46–50 However, it has been suggested that this technique could increase the risk of multifocal growth in recurrent tumors, as occurs in recurrences following cryotherapy.

Among the most recent advances is the discovery of the potential application of “old” wavelengths for the treatment of new targets. For example, long-pulse alexandrite lasers, used primarily in hair removal, can be used in the treatment of vascular lesions.51 The combination of lasers and antiangiogenic agents has also been investigated as a treatment that holds promise in the short term. One example is the use of pulsed dye lasers in combination with topical rapamycin in capillary malformations.

• •

  1565nm. A nonablative fractional laser that emits 1565nm infrared light with greater penetration than 1540 or 1550nm light has been approved, but it is still too soon to know whether it is more effective than previous lasers.

• •

  Thulium 1940nm laser. Nonablative fractional 1940nm lasers operate at a new wavelength with a water absorption coefficient that is higher than that found at other nonablative wavelengths (1410-1550nm) but lower than that of ablative lasers.

Plasma—defined as the fourth state of matter—consists of highly ionized gas that transforms into a radiating material. In fact, plasma accounts for 99% of the observable matter in the universe and is found, for example, in stars, the aurora borealis, and lightning.

Plasma can be classified as either cold or hot. Cold plasmas can be used in rejuvenation treatments to induce controlled thermal damage in the skin, which results in new collagen production and the restructuring of the dermal architecture. Cold plasma devices have also been used to improve wound healing, to induce hemostasis, and to treat infectious dermatoses, atopic dermatitis, and other conditions. Today, cold plasmas are mainly used routinely for skin rejuvenation in cosmetic dermatology.52,53

In addition to its diagnostic applications, ultrasound may have new therapeutic uses. In recent years, ultrasound cavitation has been developed for ultrasonic body contouring54 and the selective destruction of sweat glands as treatment for axillary hyperhidrosis.55,56

Several articles have underscored the utility of ultrasound as a means of enhancing the transcutaneous penetration—and therefore increasing the bioavailability—of various drugs by means of the sonophoresis effect.57–65 Other therapeutic uses of this technique involve focusing the ultrasonic waves at different depths in the skin tissue. In rejuvenation therapies, for example, due to the effect of ultrasonic waves on collagen, this technique is used to heat the dermis and cause dermal tightening.

Radiofrequency equipment is less expensive to manufacture—and therefore more accessible—than laser devices. One development in this area is the use of fractional radiofrequency devices that induce microlesions on the skin surface similar to those caused by fractional CO2 lasers. The radiofrequency energy is delivered by a roller tip that is moved across the surface of the skin. Some fractional radiofrequency devices use a system of needles to deliver the energy to deeper tissue planes.66–70

Total reflection amplification of spontaneous emission of radiation (TRASER) is a concept introduced by Morgan Gustavsson. In this technique, fluorescent dyes are excited by the sudden, flash-like release of energy, generally from a light source. After absorbing light of a precise wavelength, the fluorescent dye molecules become excited and reemit a narrow band (peak) of fluorescence at a nearby wavelength (Stokes shift phenomenon). This peak of intensity varies depending on the fluorescent dye used. TRASER is neither a laser (it lacks an optical resonator and induces non-coherent, non-collimated light) nor a pulsed light (it has no filters). TRASER is simpler than those systems and therefore less expensive to manufacture. Because it uses cheap, nontoxic, long-lasting dyes, TRASER is a very attractive technology for future development.

Through the use of different dyes, TRASER can be tuned to different wavelengths of pulsed light ranging from UV-A to near-infrared. Experiments have been carried out with various dyes, including sulforhodamine 640, which emits a peak wavelength of 658nm and has been shown to be effective in hair removal, and pyrromethene 556, which emits fluorescence with a peak of 543nm and is useful for vascular treatments. The utility of TRASER in these 2 applications has been investigated in clinical and histologic studies. This technique could have medical, domestic, and industrial uses. It will soon be seen whether TRASER is capable of replacing laser technology in a single device.71

The optical, magnetic, electronic, and fluorescent characteristics of a NP are determined by its shell. The shell can be coated with fluorescent materials that make it possible to detect the presence of the NP, which is useful for diagnostic and therapeutic purposes. If the shell is coated with certain monoclonal antibodies that have an affinity for 1 or more specific cell receptors, it could be possible to direct the NP precisely to an organ or tissue, or even to a type of cellular target (neoplastic cells, cells infected by viruses or intracellular bacteria, populations of specific inflammatory cells, etc.). It is also possible to coat the NP surface with molecules that increase the stability of the particle and prevent degradation and uptake by macrophages, thereby increasing the half-life and bioavailability of the drugs associated with the NP91 (Fig. 3).

Figure 3.

Possible modifications to the surface of nanoparticles.

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The core of a NP can be used to transport drugs, modified viruses, proteins, genetic material, vaccines, or cosmetics to precise target sites (Fig. 4).

Figure 4.

Diagram of a transport nanosystem.

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Nanoemulsions are a very promising system for administering drugs in dermatology.100 Applications include the administration of antioxidants, nonsteroidal anti-inflammatory drugs, photosensitizing agents for PDT, antimicrobial agents, and sunscreens in the form of nanoemulsions. Physical sunscreens containing titanium dioxide and iron oxide are already commercially available as topical sun protection. Because they are transparent, these sunscreens do not disperse incident light, leading to better patient acceptance and adherence.

NPs can transport a drug and, on recognizing the target, release it in response to a particular stimulus, thereby providing enormous selectivity and therapeutic precision. The vehicles of these drugs can be liposomes, polymeric NPs, or dendrimers (Fig. 5). An example is the encapsulation of minoxidil in liposomes to increase absorption in pilosebaceous follicles, thereby increasing the bioavailability of the drug in the root of the follicle. Solutions involving antioxidant vitamins encapsulated in liposomes—which increases the dermal bioavailability of the vitamins and prevents them from oxidizing on contact with air—are now commercially available. Antiandrogenic substances, finasteride, and retinoids can also be encapsulated, making it possible to reduce the side effects associated with systemic administration of these drugs.101–107

Figure 5.

Nanosystems for the transport and release of active ingredients in dermatology.

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Thanks to their photothermal properties, metallic nanostructures are candidates for use in ablative laser treatment. A laser of appropriate wavelength could be used to excite the plasmons on the metallic surface of a nanostructure consisting of a metallic shell over a glass surface, producing heat. This technology could revolutionize light-source-based therapies, mainly those which involve red or near-infrared light, which is capable of penetrating tissues to a depth of several centimeters.

By using appropriate surface molecules (antibodies), it could be possible to select specific molecular targets that would allow the selective thermal destruction of malignant cells and/or the blood vessels supporting the skin tumor. In therapeutics, it could be possible to use lasers or light sources on any area of the skin surface and target cell populations that do not contain any of the classic chromophores. In mice, gold NPs conjugated with anti-EGFR antibodies have been used in the treatment of squamous cell carcinoma to destroy malignant cells with half the energy required for benign cells. Selective photothermal ablation of melanomas has also been achieved in mice using gold NPs attached to a peptide that is an agonist for the melanocortin 1 receptor overexpressed in melanoma.108–113

Carbon nanotubes—molecules in the fullerene family consisting of sheets of graphite arranged in a tubular structure—also absorb light in the near-infrared spectral range and are capable of generating heat. As in the case of NPs, it could be possible to take advantage of the fact that, due to their greater permeability, carbon nanotubes accumulate in the tumor stroma through the capillary vessels that form in order to nourish the tumor. Following the application of a laser or other light source, the tumor could be destroyed by photoablation.114–116

Cutaneous vascular lesions such as telangiectasias and capillary malformations are another interesting area for exploration. If metallic nanostructures are designed that are capable of accumulating in the periphery or endothelial coating of these lesions, photothermal ablation could be used thanks to the surface plasmonic properties of the nanostructures following irradiation with a light energy source.

NPs can act as biosensors that allow the adjustment of dosage and treatment regimen, thereby reducing systemic toxicity without relinquishing the maximum therapeutic effect.

As the reader may have deduced, research on the biomedical applications of nanotechnology is filled with possibilities for improving techniques for diagnosis, monitoring and treatment in dermatology. This field is poised to revolutionize our specialty in the coming decades.

The development of new technologies is inseparable from the appearance of new toxicities that affect both patients and health care workers. Gas chromatography–mass spectrometry studies of smoke plumes from laser hair removal have demonstrated the presence of more than 14 potentially toxic substances including 2-methylpyridine, diethyl phthalate, and trimethyl disulfide.117

As new technologies with therapeutic and, especially, cosmetic applications have spread and demand for them has grown, these techniques have been widely and almost indiscriminately applied to all sorts of skin lesions before their real possibilities and side effects are fully understood.

The high reactivity of NPs could also alter other biological mechanisms besides those identified during the design of the particles; this phenomenon has become known as nanotoxicity. NPs could also become new irritants and allergens. Quantum dots contain heavy metals and could therefore have cytotoxic effects, especially if they are not designed with a hydrophilic coating. Moreover, they remain inside the cells for weeks or months, and we know almost nothing about their excretion pathways or how they are metabolized. In fact, some nonbiodegradable particles could remain in the body indefinitely and cause permanent activation of the immune system as the body attempts to eliminate them, possibly triggering autoimmune diseases. The following factors are essential to determining the safety profile of NPs118:

• 1)

  How the NP enters the body.

• 2)

  Size (the smaller the NP, the more toxic it is).

• 3)

  Biocompatibility.

• 4)

  Biodegradability.

Therefore, in our opinion and that of experts, more exhaustive studies are needed to ensure the safety of these techniques.

Scientific and technical advances are gradually making their way into the routine practice of dermatologists. Concepts and terms that are strange to us today may become the standard diagnostic and therapeutic methods of tomorrow. We have reviewed some recent advances that are currently experimental or have limited applications, but which in the future could complement or even replace present techniques.