Lasers Med Sci (2008) 23:217–228
DOI 10.1007/s10103-007-0470-x
REVIEW ARTICLE
Plasmonic photothermal therapy (PPTT)
using gold nanoparticles
Xiaohua Huang & Prashant K. Jain & Ivan H. El-Sayed &
Mostafa A. El-Sayed
Received: 26 April 2007 / Accepted: 10 May 2007 / Published online: 3 August 2007
# Springer-Verlag London Limited 2007
Abstract The use of lasers, over the past few decades, has
emerged to be highly promising for cancer therapy
modalities, most commonly the photothermal therapy
method, which employs light absorbing dyes for achieving
the photothermal damage of tumors, and the photodynamic
therapy, which employs chemical photosensitizers that
generate singlet oxygen that is capable of tumor destruc-
tion. However, recent advances in the field of nanoscience
have seen the emergence of noble metal nanostructures
with unique photophysical properties, well suited for
applications in cancer phototherapy. Noble metal nano-
particles, on account of the phenomenon of surface
plasmon resonance, possess strongly enhanced visible and
near-infrared light absorption, several orders of magnitude
more intense compared to conventional laser phototherapy
agents. The use of plasmonic nanoparticles as highly
enhanced photoabsorbing agents has thus introduced a
much more selective and efficient cancer therapy strategy,
X. Huang : P. K. Jain : M. A. El-Sayed (*)
Laser Dynamics Laboratory,
School of Chemistry and Biochemistry,
Georgia Institute of Technology,
Atlanta, GA 30332-0400, USA
e-mail: melsayed@gatech.edu
I. H. El-Sayed
Department of Otolaryngology—Head and Neck Surgery,
Comprehensive Cancer Center,
University of California at San Francisco,
San Francisco, CA 94143, USA
M. A. El-Sayed
University of California,
Berkeley, CA 94720, USA
viz. plasmonic photothermal therapy (PPTT). The synthetic
tunability of the optothermal properties and the bio-
targeting abilities of the plasmonic gold nanostructures
make the PPTT method furthermore promising. In this
review, we discuss the development of the PPTT method
with special emphasis on the recent in vitro and in vivo
success using gold nanospheres coupled with visible lasers
and gold nanorods and silica–gold nanoshells coupled with
near-infrared lasers.
Keywords Surface plasmon resonance (SPR) .
Plasmonic photothermal therapy (PPTT) . Cancer .
Gold nanospheres . Gold nanorods . Gold nanoshells .
Immunotargeting
Introduction
The use of heat has become one of the major methods
for tumor therapy since its ancient usage in 1700 BC
when a glowing tip of a firedrill was used for breast cancer
therapy [1]. Later heating sources ranging from radio-
frequency [2–5] to microwaves [6–9] as well as ultrasound
waves [10–12] were introduced to induce moderate heating
in a specific target region, which is termed as hyperthermia.
Hyperthermia is commonly defined as heating tissue to a
temperature in the range 41–47°C for tens of minutes [13].
Tumors are selectively destroyed in this temperature range
because of their reduced heat tolerance compared to normal
tissue, which is due to their poor blood supply. Hyper-
thermia causes irreversible cell damage by loosening cell
membranes and denaturing proteins. But the applications of
the heating sources conventionally employed for hyperther-
218
mia are limited because of their damage to surrounding
healthy tissues.
A revolution in cancer therapy has taken place by the
emerging use of laser light to achieve controlled and
confined thermal damage in the tumor tissue. Laser, the
acronym for light amplification by the stimulated emission
of radiation [14], is an optical source that emits photons in a
coherent and narrow beam. It was proposed in 1959 [14]
and first demonstrated in 1960 [15]. Laser usage in surgery
was first reported by ophthalmologists in 1963 [16] and
then reported for tumor eradication in 1965 [17] followed
by wide interest in late 1960s [18–20]. The laser light,
usually neodymium–yttrium aluminum garnet (Nd–YAG,
1.06 um) and CO2 laser (10.6 um) [21–25] can either be
transmitted from optical fiber tip to exposed tumors in the
air or delivered into a confined space by inserting the bare
end of the fiber into the center of the target tumor, which is
often called interstitial laser hyperthermia [26–30]. Laser
light has the characteristics of monochromaticity, coher-
ence, and collimation [31–33]. These properties provide a
narrow beam of high intensity, which transmits deep down
into the target tissue with minimal power loss and great
precision. The biggest disadvantage of laser therapy is its
nonselectivity. Both normal and tumor cells in the path of
the laser light are damaged. The requirement of the high
power density is another problem. High power laser output
up to tens to hundreds of watts has to be used to efficiently
induce the tumor oblation [23].
Another type of tumor therapy method is the photody-
namic therapy (PDT), also known as photochemotherapy
[34–41], which involves cell destruction caused by means
of toxic singlet oxygen and/or other free radicals that are
produced from a sequence of photochemical and photobi-
ological processes. These processes are initiated by the
reaction of a photosensitizer with tissue oxygen upon
exposure to a specific wavelength of light in the visible or
near-infrared (NIR) region. The earliest sensitizer used was
acridine, which was reported in 1900 to kill paramecia [42]
and followed by eosin for skin cancer treatment in 1903
[43]. Although many chemicals have been later reported for
photochemical therapy, porphyrin-based sensitizers [44–49]
lead the role in clinical applications because of their
preferential retention in cancer tissues and due to the high
quantum yields of singlet oxygen produced. The Photofrin®
[50], which is a purified hematoporphyrin derivative, has
been approved for clinic trials by the US Food and Drug
Administration. Porphyrin-based therapy can only be used
for tumors on or just under the skin or on the lining of
internal organs or cavities because it absorbs light shorter
than 640 nm in wavelength. For deep-seated tumors,
second generation sensitizers, which have absorbance in
the NIR region, such as core-modified porphyrins [51],
chlorins [52] phthalocyanine [53], and naphthalocyanine
Lasers Med Sci (2008) 23:217–228
[54], have been introduced. A major drawback of PDT is
that the photosensitizing drug stays in the body for a long
time, rendering the patient to be highly sensitive to light.
An alternative to PDT is the photothermal therapy
(PTT) in which photothermal agents are employed to
achieve the selective heating of the local environment
[55–61]. When the PTT agents absorbs light, electrons
make transitions from the ground state to the excited state.
The electronic excitation energy subsequently relaxes
through nonradiative decay channels. This results in the
increase in the kinetic energy leading to the overheating of
the local environment around the light absorbing species.
The heat produced can be employed for local cell or tissue
destruction [62–65]. The photoabsorbing agents can be
natural chromophores in the tissue [66–71] or externally
added dye molecules such as indocyanine green [72, 73],
naphthalocyanines [74], and porphyrins coordinated with
transition metals [75]. Natural chromophores, however,
suffer from very low absorption. The choice of the
exogenous photothermal agents is made on the basis of
their strong absorption cross sections and highly efficient
light-to-heat conversion. This greatly reduces the amount of
laser energy required to achieve the local damage of the
diseased cells, rendering the therapy method less invasive.
But the problem with dye molecules is their photobleaching
under laser irradiation.
In recent years, the tremendous development of nano-
technology has provided a variety of nanostructures with
unique optical properties that are useful in biology and
biomedicinal applications [76–83]. From the point of the
view of cancer therapeutics, noble metal nanoparticles
become very useful as agents for PTT on account of their
enhanced absorption cross sections, which are four to five
orders of magnitude larger than those offered by conven-
tional photoabsorbing dyes. This strong absorption ensures
effective laser therapy at relatively lower energies rendering
the therapy method minimally invasive. Additionally, metal
nanostructures have higher photostability, and they do not
suffer from photobleaching. Currently, gold nanospheres
[84–91], gold nanorods [92–95], gold nanoshells [96–99],
gold nanocages [100, 101], and carbon nanotubes [102] are
the chief nanostructures that have been demonstrated in
photothermal therapeutics due to their strongly enhanced
absorption in the visible and NIR regions on account of
their surface plasmon resonance (SPR) oscillations. Of
these structures, the first three nanostructures (see Fig. 1)
are especially promising because of their ease of prepara-
tion, ready multi-functionalization, and tunable optical
properties. In the present review, we discuss the photo-
thermal properties of these plasmonic nanostructures and
their application in selective PTT. We propose the name
plasmonic photothermal therapy (PPTT) for this treatment
to distinguish it from PTT and PDT.
Lasers Med Sci (2008) 23:217–228
Fig. 1 Plasmonic gold nanostructures commonly used for PPTT. a
Nanospheres (transmission electron microscopy [TEM] image repro-
duced with permission from [110]; b nanorods (TEM image
Photothermal properties of plasmonic gold
nanoparticles
In 1857, Faraday [103] made colloidal gold for the first
time by reducing gold chloride with phosphors and
recognized that the reddish color was due to the small size
of the colloidal gold particles. In 1951, Turkevich et al.
[104] simplified the method by using sodium citrate as
reducing agents. Since then, the interaction between light
and gold nanoparticles has been widely studied [105–112].
Gold nanoparticles absorb light strongly in the visible
region due to the coherent oscillations of the metal
conduction band electrons in strong resonance with visible
frequencies of light. This phenomenon is known as the SPR
[105–113]. The SPR frequency is dependent on the type of
the metal, the size and shape of the metal nanoparticles, as
well as the dielectric constant of the surrounding medium,
thus imparting a unique optical tunability to the nanostruc-
tures. When the size increases, the surface plasmon ab-
sorption maximum slightly redshifts (Fig. 2a). When the
nanoparticles form assemblies or aggregates, the surface
plasmon absorption maximum redshifts to the NIR region.
Interestingly, when the shape of the gold nanoparticles is
changed from sphere to rod, the SPR spectrum splits into
two bands: a stronger long-wavelength band in the NIR
region due to the longitudinal oscillation of electrons and a
weaker short-wavelength band in the visible region around
219
reproduced with permission from [115]); c Nanoshells (TEM image
reproduced with permission from [97])
520 nm due to the transverse electronic oscillation [109,
111, 112, 114–118]. Unlike spherical nanoparticles, the
absorption spectrum of the gold nanorods is very sensitive
to the aspect ratio (length/width). With an increase in the
nanorod aspect ratio, the SPR absorption wavelength
maximum of the longitudinal band significantly redshifts
(Fig. 2b). Similarly, when the solid gold nanospheres are
changed to gold shell structures, the absorption maximum
also greatly redshifts. In 1998, Halas and coworkers at Rice
University [119] developed the gold nanoshell structure,
which is composed of a silica core (100–200 nm in diameter)
surrounded by a thin layer of gold shells (5–20 nm). The
nanoshells absorb and scatter strongly in the NIR region
[120]. The optical resonance of the nanoshells can be tuned
by adjusting the ratio of the thickness of the gold shell to
the diameter of the silica core (Fig. 2c). It has been shown
that the smaller this ratio, the more redshifted is the SPR
wavelength [97].
The photothermal properties of gold nanoparticles have
been systematically studied using femtosecond transient
absorption spectroscopy by Link and El-Sayed [111], who
have shown that the photoexcitation of metal nanostruc-
tures results in the formation of a heated electron gas that
subsequently cools rapidly within ∼1 ps by exchanging
energy with the nanoparticle lattice. This is followed by
phonon–phonon interactions where the nanoparticle lattice
cools rapidly by exchanging energy with the surrounding
220
Fig. 2 Size, shape, and composition dependence of the surface plasmon
absorption spectrum of plasmonic gold nanostructures. a Nanospheres of
different sizes (reproduced with permission from [110]); b nanorods of
different aspect ratios (reproduced with permission from [118]); c nano-
shells of different shell thicknesses (reproduced with permission from
[97])
medium on the timescale of ∼100 ps. This fast energy
conversion and dissipation can be readily used for the
heating of the local environment by using light radiation
with a frequency strongly overlapping with the nanoparticle
SPR absorption band. The intense SPR-enhanced absorp-
tion of gold nanoparticles makes the photothermal conver-
sion process highly efficient. The absorption cross section
of gold nanoparticles [121] is typically four to five orders
of magnitude stronger than the strongest absorbing Rhoda-
Lasers Med Sci (2008) 23:217–228
mine 6G dye molecules [122]. Hot electron temperatures of
several thousand kelvins are easily reached in the nano-
particles even with laser excitation powers as low as 100 nJ
and the lattice temperature on the order of a few tens of
degrees can be achieved [111]. This highly efficient pro-
duction of heat energy from the absorbed light energy by
gold nanoparticles make them greatly promising in the
PPTT of cancers and other diseases. Further, in the case of
gold nanorods and gold nanoshells, this strong absorption can
be tuned to the NIR region (Fig. 2b,c), a region where light
penetration is optimal due to minimal absorption from tissue
chromophores and water [123]. This makes NIR-resonant
gold nanostructures very useful for clinical therapy applica-
tions involving tumors located deep within bodily tissue.
In addition to the local heating of the surrounding
environment, which leads to irreversible cell destruction
through protein denaturation and coagulation as well as cell
membrane destruction, bubble formation around gold
nanoparticles is also involved in the case of short pulse
laser irradiation, which imposes mechanical stress leading
to cell damage. Irradiation with short laser pulses has been
shown to lead to the rapid heating of the particles and va-
porization of a thin layer of fluid surrounding each particle,
producing a microscopic version of underwater explosion
and cavitation bubble formation [84–86, 88, 124, 125].
Zharov et al. [88] also found that nanoclusters formed by the
assembly of gold nanoparticles on human breast cancer cells
significantly enhance the bubble formation causing more
efficient cancer cell killing.
Very recently Khlebtsov et al. theoretically simulated the
photothermal conversion efficiency of the different nano-
structures including gold nanospheres, gold nanorods, gold
nanoshells, linear chains, 2D arrays, and 3D clusters [91]
by calculating their SPR absorption spectra. It was found
that gold spheres with diameters of about 30–40 nm are
most preferable, as their normalized absorption is maximal
in the visible spectrum region. The nanorods with length
between 15 and 70 nm were predicted to be most efficient.
Of course, it would also be required that the longitudinal
absorption maximum be matched to the wavelength of the
NIR laser to get optimal photothermal efficiency. Gold
nanoshells with external diameters of about 50–100 nm and
gold shell thicknesses of about 4–8 nm are estimated to be
the most effective due to the strong absorption and low
scattering near 800 nm.
Bioconjugation and targeting
Most laser-based therapeutic methods rely on the use of
endoscopes and fiber optic catheters to deliver light
specifically to the tumor region and intravenously admin-
Lasers Med Sci (2008) 23:217–228
istered photosensitizers/absorbers to achieve selectivity.
However, the use of immunotargeting strategies to deliver
the photodynamic or photothermal agents selectively to the
diseased cells and tissue offers an efficient route to
achieving selectivity and reducing nonspecific injury to
healthy cells. Metal, especially gold, nanoparticles allow
easy biofunctionalization, thus making them promising for
integration with immunotargeting strategies.
The selectivity of gold nanostructures for photothermal
cancer therapy has been demonstrated by their functional-
ization with specific tumor-targeting molecules. Two
targeting strategies are commonly used. One involves
nanoparticles passivated by poly (ethylene) glycol (PEG),
and the other employs nanoparticles conjugated to anti-
bodies specific to biomarkers on the diseased cells. PEG is
used to increase the biocompatibility and biostability of
nanoparticles and impart them an increased blood retention
time. Citrate-capped gold nanospheres, cetyl trimethylam-
monium bromide (CTAB)-capped gold nanorods, as well as
gold nanoshells have poor stability when they are dispersed
in buffer solution due to the aggregating effect of salt ions.
By capping the nanoparticles with PEG, the biocompatibil-
ity is greatly improved, and nanoparticle aggregation is
prevented. PEGylated nanospheres and nanorods can be
readily made by the conjugation of thiol-functionalized
PEG with the gold nanoparticles [126, 127]. In case of in
vivo applications, PEGylated nanoparticles are preferen-
tially accumulated into tumor tissues due to the enhanced
permeability and retention effect, known as the “golden
standard” for drug design [128–135]. Compared to normal
tissue, the blood vessels in tumor tissue are more leaky, and
thus, macromolecular or polymeric molecules preferentially
extravasate into tumor tissue. Due to the decreased
lymphatics, the tumor tissue retains large molecules for a
longer time, whereas normal tissue quickly clears out the
external particles. This tumor targeting method is called
passive targeting as against the antibody-targeting method
[128–135].
The antibody based targeting is more active, specific and
efficient. The antibodies are selected to target a specific
tumor marker. For instance, anti-epidermal growth factor
receptor (EGFR) antibodies can be employed to target
overexpressed EGFR on oral cancer cells [89, 90, 92] and
cervical cancer cells [136, 137], anti-Her2 for overex-
pressed Her2 on breast cancer cells [99] and seprase on
breast cancer cells [88]. The binding of antibodies to gold
nanospheres was first reported in the 1950s when anti-
bodies were used for the staining of cellular components by
electron microscopy [138]. The antibodies are generally
bound to negatively charged citrate-capped gold nano-
spheres by nonspecific interactions by adjusting the pH of
the colloidal solution to be just above the isoelectric point
(pI, zero net charge of the protein) of the antibody such that
221
the antibody has an small net negative charge. The anti-
bodies are thus nonspecifically adsorbed onto gold nano-
particles while still keeping the nanoparticles negatively
charged, providing stability in colloidal solution. In recent
years, Sokolov et al. [136, 137] used this method to bind
anti-EGFR to gold nanospheres, which were then used as
optical labels to detect the overexpressed EGFR on ovarian
cancer cells by light scattering imaging using a single
wavelength laser. El-Sayed et al. [139] used the same
method to bind anti-EGFR to gold nanospheres and realized
both diagnostics using dark field microscopy and therapy of
oral cancer cells using a 514 nm argon ion laser [89].
Gold nanorods are capped with CTAB molecules, which
are positively charged [140]. As antibodies are slightly
negatively charged at pH=7.4, antibodies can be adsorbed
onto gold nanorods by electrostatic interactions. However,
this causes particle aggregation in solution due to the
neutralization of the surface charge. For the binding of
antibodies to gold nanorods solution, the surface charge is
reversed by adsorption of a PSS− layer [141, 142]. Then,
the antibodies are adsorbed onto the PSS− layer probably
by hydrophobic interactions while still stabilizing the
nanorods by the negative charge on the antibodies [141,
142]. Figure 3a shows the scheme of the antibody binding
to gold nanorods through a PSS bridging layer.
Another method is the use of chemical binding between
a functional group on the antibodies and the metal surface
of the nanoparticles [143]. The covalent binding of the thiol
group to gold is used very commonly for nanoparticle
surface bioconjugation. In the work by Liao et al. [126] the
antibodies were bound to nanorods with a long chain
succinimidyl 6-[3′-[2-pyridyldithio]-propionamido] (LC-
SPDP) cross-linker hexanoate (see Fig. 3b). LC-SPDP con-
sists of a pyridildithio group that binds to the gold nanorod
surface, and an N-hydroxysuccinimide (NHS) ester, which
binds to the primary amines in the antibodies.
For nanoshell bioconjugation [99], antibody molecules
are first bound to a PEG linker orthopyridyl-disulfide
(OPSS)–PEG–NHS through an amidohydroxysuccinimide
group (NHS). The antibody-PEG linker complex is then
attached to the nanoshell surface through the sulfur-contain-
ing OPSS group located at the distal end of the PEG linker.
In addition to antibodies, folic acid can also be used for
active tumor targeting because cancer cells require exces-
sive folic acid, which is a ligand for folate receptors [95,
102, 144, 145]. Wei and coworkers [95] have conjugated
folate ligands with oligoethyleneglycol spacers to gold
nanorods by in situ dithiocarbamate formation. The folate-
conjugated gold nanorods were found to specifically bound
to the surface of KB cancer cells. Thus, there exist a variety
of surface chemistry techniques that can be utilized for
designing biofunctionalized nanoparticles targeted to the
disease biomarker of choice.
222
PPTT by visible lasers
In 1999, Lin et al. [125] first reported the selective PTT
based on the use of light-absorbing microparticles that
absorb light in the visible region. In 2003, they demon-
strated selective PPTT using gold nanoparticle immuno-
conjugates [84]. Lymphocytes incubated with gold
nanoparticles conjugated to antibodies and then exposed
to short laser pulses (565 nm wavelength, 20 ns duration)
showed cell death with 100 laser pulses at an energy of
0.5 J/cm2. The cell death is attributed mainly to the
cavitation bubble formation around the nanoparticles. By
adjusting the particle number, size, and laser energy, the
researchers were able to selectively induce cell death or
transiently modify cellular functions without causing cell
destruction. In the same year, Zharov et al. [85] studied the
threshold and the dynamics of thermal events around the
particles incorporated into K562 cancer cells using nano-
second Nd–YAG laser at 532 nm and a photothermal
contrast technique. They found that, at an energy level of
2–3 J/cm2, only one or three laser pulses are sufficient to
damage a cell containing 10–15 particles of 20 nm size,
whereas at a lower fluence rate of 0.5 J/cm2, at least 50
pulses and approximately 100 particles are required to
produce the same harmful effects on the cells.
Recently, El-Sayed and coworkers [89, 90] demonstrated
selective PPTT by using gold nanoparticles with a visible
continuous wave (CW) laser. In these studies, 40 nm gold
nanoparticle were conjugated to anti-EGFR antibodies and
then incubated with both human oral cancer cells and
nonmalignant skin cells for 30 min. By using dark field
light scattering imaging and surface plasmon absorption
Fig. 3 Antibody conjugation of
gold nanorods. a Gold nanorods
are coated with PSS polyelec-
trolytes and antibodies are
adsorbed onto PSS by nonspe-
cific interactions; b antibodies
are covalently bound to the rod
surface by LC-SPDP crosslinker
(reproduced with permission
from [126])
Lasers Med Sci (2008) 23:217–228
spectroscopy, it was found that gold nanoparticles were
preferentially and specifically bound to the cancer cells,
while only a heterogeneous nonspecific distribution of the
nanoparticles was seen over the healthy cells [139]. The
nanoparticle-labeled cells were then exposed to a CW argon
ion laser at 514 nm [89]. It was found that the malignant
cells required less than half the laser energy to be killed as
compared to the benign cells (see Fig. 4, [89]). No
photothermal destruction was observed for any of the cell
types without nanoparticle labeling, even at four times the
energy required to kill the malignant cells labeled with anti-
EGFR/gold nanoparticle conjugates. This selective photo-
damage of the cancer cells is clearly attributed to the higher
gold nanoparticle loading on cancer cells due to the
overexpressed EGFR on the cancer cell surface. Higher
gold nanoparticle labeling results in a consequently higher
optical density. Thus, a lower laser energy is required to
raise the temperature above the threshold for destruction, as
estimated to be in the range of 70–80°C [90]. This method
can be extended to other types of cancers as well because
most types of cancer cells have an overexpression of EGFR
receptors. However, the use of visible light absorbing
nanospheres is restricted to skin or near-surface type
cancers due to the inability of visible light to penetrate
through skin and tissue.
PPTT by NIR lasers
For in vivo therapy for tumors under skin and deeply seated
within tissue, NIR light is required because of its deep
penetration due to minimal absorption of the hemoglobin
Lasers Med Sci (2008) 23:217–228 223

Fig. 4 Selective PPTT for can-

cer cells by using anti-EGFR
conjugated gold nanospheres
(reproduced with permission
from [89]). After incubation
with anti-EGFR conjugated gold
nanoparticles, HaCat normal
cells are destroyed at a laser
power threshold of 57 W/cm2,
while HSC and HOC cancer
cells are destroyed at much
lower thresholds of 25 and
19 W/cm2, respectively. The
difference reflects the much
larger density of anti-EGFR
conjugated gold nanospheres on
the surface of the cancer cells
compared to that on the normal
cells due to the selective target-
ing of EGFR overexpressed on
cancer cells

and water molecules in tissues in this spectral region.
Carbon nanotubes have optical absorbance in the NIR
window [146] and, thus, have potential for NIR PTT. Dai
and coworkers [102] achieved selective cancer cell
destruction by the functionalization of single-walled carbon
nanotubes with a folate moiety that selectively targets the
folate receptors on tumor cells, while the receptor-free
normal cells are unaffected.
Gold nanorods and nanoshells have been demonstrated
for selective PPTT using CW NIR lasers mainly by the El-
Sayed [92] and Halas groups [96, 99], respectively. By
using dark-field light scattering imaging, El-Sayed and
coworkers found that gold nanorods conjugated to anti-
EGFR antibodies were well organized on the surface of
cancer cells with relatively higher binding affinity, while
they were randomly distributed nonspecifically on and
around the normal cells, similar to the case of the gold
nanospheres [92, 139]. A CW Ti:Sapphire laser with a
wavelength at 800 nm, overlapping with the SPR absorp-
tion wavelength maximum of gold nanorods at 800 nm,
was used for the photoirradiation of the cells labeled with
the nanorods. It was found that the cancer cells required
half the laser energy (10 W/cm2) to be photothermally
damaged as compared to the normal cells (20 W/cm2), as
attributed to the selective targeting of the overexpressed
EGFR on the cancer cell surface by the anti-EGFR-
conjugated gold nanorods (Fig. 5).
Later, Takahashi et al. [93] in Japan achieved cell death
using phosphatidylcholine-passivated gold nanorods and a
pulsed Nd–YAG laser at 1,064 nm. Recently, Wei and
coworkers at Purdue University [95] demonstrated that gold
nanorods conjugated to folate ligands can be used for
hyperthermic therapy of KB oral cancer cells with a CW
Ti:Sapphire laser. Severe blebbing of cell membranes
was observed at laser irradiation with power density as
low as 30 J/cm2.
The work by Halas and coworkers has shown that gold
nanoshells can be used for PPTT in the NIR region by both
passive cancer targeting using PEG-conjugated nanoshells
[96–98] and active targeting using antibody-conjugated
nanoshells [99]. In the antibody case [99], gold nanoshells
conjugated through PEG linkers to anti-Her2 antibodies
were employed for targeting breast cancer cells. A diode
laser at 820 nm was used for photothermal heating (7 min)
of the labeled cells (Fig. 6). Only the cancer cells incubated
with the antibody conjugated gold nanoshells were dam-
224 Lasers Med Sci (2008) 23:217–228

Fig. 5 Selective PPTT for can-

cer cells in the NIR region by
using anti-EGFR conjugated
gold nanorods (reproduced with
permission from [92]). After
incubation with anti-EGFR con-
jugated gold nanorods, HaCat
normal cells are destroyed at a
laser power threshold of 20 W/
cm2, while HSC and HOC can-
cerous cells are destroyed at a
much lower threshold of 10 W/
cm2. The difference reflects the
much larger density of gold
nanorods on the surface of the
cancer cells compared to that on
the normal cells

aged under the laser irradiation. In the PEG case [96], the in vivo. For in vivo therapy, the researchers achieved
researchers demonstrated successful PTT both in vitro and successful targeting using the PEGylated gold nanoshells
Fig. 6 Selective PPTT for can-
cer cells by using anti-Her2
antibody conjugated gold nano-
shells (reproduced with permis-
sion from [99]). Only the cells
incubated with anti-Her2 anti-
body conjugated gold nano-
shells are damaged under NIR
irradiation
Lasers Med Sci (2008) 23:217–228
injected directly into the tumor region [96] or delivered
intravenously [98]. It was shown that NIR light of 820 nm
at 4 W/cm2 caused irreversible tumor tissue damage. Most
notably, these studies show that laser dosages required to
induce tissue damage using the plasmonic gold nano-
structures are 10- to 25-fold lower than those used in
studies employing photoabsorbing dyes such as indocya-
nine green dye.
Summary
Plasmonic gold nanostructures thus show great promise for
the selective PTT for cancer as well as other diseases. We
propose the name PPTT for this treatment. It is realized that
a number of variables need to be further addressed, e.g.,
stability, biocompatibility, and chemical reactions of nano-
particle bioconjugates in physiological environments, blood
retention time, tumor extravasation, the fate of the nano-
particles following therapy, etc. We anticipate that the
success and promise of the initial use of plasmonic
nanoparticles for selective PPTT could be efficiently
extended to clinical stage once the optimal parameters of
these variables are identified, as is being done through
current research studies.
Acknowledgment We thank the financial support of NCI Center of
Cancer Nanotechnology Excellence (CCNE) Award (U54CA119338).
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