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REVIEW

Photonanodermatology: the interface of photobiology, dermatology and

nanotechnology
Jamie Hia1 & Adnan Nasir2
1
Department of Biology, and 2Department of Dermatology, UNC Chapel Hill, Chapel Hill, NC, USA

Summary

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

Correspondence:
Adnan Nasir, Department of Dermatology, UNC
Chapel Hill, 3100 Thurston Bowles Building, Chapel
Hill, NC 27514, USA.
e-mail: anasir@pol.net

Accepted for publication:

1 July 2010

Conflicts of interest:
None declared.

N anotechnology 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
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,

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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 encom-
passes nanomaterials, nanodevices, and nanostructures (2). In
dermatology, the greatest advances in nanotechnology have been
in nanomaterials such as nanoparticles for drug delivery. Nano-
particles 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
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
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Photonanodermatology
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 sun-
screens with better consumer acceptance, and possibly,
compliance. There is a theoretic concern that nanoparticulate
sunscreens may be more reactive, especially through the gene-
ration 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 nanopar-
ticulate 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
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
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Hia & Nasir
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
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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 res-
ponse (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 deve-
loped 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
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Photonanodermatology
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
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
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Hia & Nasir
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
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
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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. surround-
ing tissue was not carried out in this study, another study using
gold nanoshells to treat breast cancer showed temperatures
elevations to 61 1C and temperature increases of 25–30 1C up to
a depth of 3 cm from the surface of the skin. Selective photo-
thermolysis 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
r 2011 John Wiley & Sons A/S  Photodermatology, Photoimmunology & Photomedicine 27, 2–9
16000781, 2011, 1, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/j.1600-0781.2010.00536.x by Cochrane Mexico, Wiley Online Library on [14/11/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Photonanodermatology
drawbacks. Other techniques to reduce toxicity include purer
manufacture, reduction in heavy metal contamination, reduction
of oxidative potential, enhancement of biodegradation and bio-
elimination, 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
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 superhy-
drophobicity, 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
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.
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