Photothermal Efficiencies of Nanoshells and Nanorods for Clinical

Jun 11, 2009 - in the direct vicinity of the nanoparticles undergo hyperthermia and death, resulting in drug-free tumor remission.7,10. As this effect...
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Photothermal Efficiencies of Nanoshells and Nanorods for Clinical Therapeutic Applications Joseph R. Cole,†,| Nikolay A. Mirin,‡,| Mark W. Knight,†,| Glenn P. Goodrich,⊥ and Naomi J. Halas*,†,‡,§,| Department of Electrical and Computer Engineering MS-366, Department of Chemistry MS-60, Department of Bioengineering MS-142, and Laboratory for Nanophotonics, Rice UniVersity, 6100 Main Street, Houston, Texas 77005, and Nanospectra Biosciences, Inc., 8285 El Rio Street, Suite 150, Houston, Texas 77054 ReceiVed: January 13, 2009; ReVised Manuscript ReceiVed: May 7, 2009

With clinical trials for photothermal tumor ablation using laser-excited tunable plasmonic nanoparticles already underway, increasing understanding of the efficacy of plasmonic nanoparticle-based photothermal heating takes on increased urgency. Here we report a comparative study of the photothermal transduction efficiency of SiO2/Au nanoshells, Au2S/Au nanoshells, and Au nanorods, directly relevant to applications that rely on the photothermal response of plasmonic nanoparticles. We compare the experimental photothermal transduction efficiencies with the theoretical absorption efficiencies for each nanoparticle type. Our analysis assumes a distribution of randomly oriented nanorods, as would occur naturally in the tumor vasculature. In our study, photothermal transduction efficiencies differed by a factor of 3 or less between the different types of nanoparticle studied. Both experiment and theory show that particle size plays a dominant role in determining transduction efficiency, with larger particles more efficient for both absorption and scattering, enabling simultaneous photothermal heating and bioimaging contrast enhancement. I. Introduction The technological impact of plasmonic nanoparticles in fields such as medicine,1-3 sensing,2,3 and advanced functional materials and devices4-6 is imminent. Clinical trials are currently underway to test tunable plasmonic particles such as nanoshells and nanorods as photothermal cancer therapies.7-9 This type of therapy exploits the fact that the nanoparticle resonance can be tuned to the infrared “water window” where biological tissue is highly transparent. Nanoparticles are injected into the bloodstream and accumulate at tumor sites, where they heat their local environment when irradiated with laser light whose wavelength coincides with the resonant wavelength of the nanoparticle. Adjacent healthy tissue without embedded nanoparticles is unaffected by the laser light alone, but cancer cells in the direct vicinity of the nanoparticles undergo hyperthermia and death, resulting in drug-free tumor remission.7,10 As this effect transitions from the research laboratory to clinical applications, it is important to identify which nanoparticle sizes and shapes meet the requirements of this type of application. A strong absorption cross section, leading to efficient photothermal heating in the direct vicinity of the nanoparticle in a physiologically compatible wavelength range, is critically important. Other nanoparticle properties are also important to consider, however. Light scattering, for example, which does not lead to local heating but does allow the observer to easily locate the presence of nanoparticles and hence is a highly desirable property for providing contrast in bioimaging applications, needs to be considered. Both absorption and * To whom correspondence should be addressed. E-mail: [email protected]. Phone: 713-348-5746. Fax: 713-348-5686. † Department of Electrical and Computer Engineering, Rice University. ‡ Department of Chemistry, Rice University. § Department of Bioengineering, Rice University. | Laboratory for Nanophotonics, Rice University. ⊥ Nanospectra Biosciences, Inc.

scattering cross sections depend on nanoparticle size for any given nanoparticle shape.11,12 In addition to optical properties, the size and shape of candidate nanoparticles for therapeutic applications may determine their tumoral or intracellular uptake, as well as their post-treatment biodistribution. Thus a study and analysis of the transfer of optical energy into heat by nanoparticles of potential use in clinical therapies is an important first step in the ultimate selection of which nanoparticles may best be suited for the development of any specific therapeutic application. Here we investigate how the physical properties of three different types of plasmonic nanoparticlessAu/SiO2 nanoshells, Au/Au2S nanoshells, and Au nanorodsscould be advantageous in photothermal cancer therapy. By use of a controlled thermal environment, we measure the photothermal transduction efficiency of these three types of nanoparticles and compare it to their absorption efficiency as calculated by Mie theory for nanoshells and the finite element method (FEM) for nanorods. These measurements provide important quantitative metrics for understanding how photothermal heating efficiencies are controlled by nanoparticle size and shape. II. Experimental Methods Electromagnetic Simulations. To estimate the photothermal transduction efficiency of our three nanoparticle species we calculate their effective extinction, absorption, and scattering cross sections. The ratio of the absorption to extinction cross section is the fraction of luminous energy that the nanoparticles are expected to convert to thermal energy. We refer to this ratio as the absorption efficiency, and it should be equal to the photothermal transduction efficiency in the absence of any physical effects that may alter the electromagnetic response of the nanoparticle, such as nanoparticle aggregation. For spherically symmetric nanoparticles such as the Au/ Au2S or Au/SiO2 nanoshells used in these experiments, the

10.1021/jp9003592 CCC: $40.75  2009 American Chemical Society Published on Web 06/11/2009

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Cabs )

2 n√ε0/µ0 | F E inc | 2

∫ UavdV

(1)

Here, Uav is the power absorbed by the particle in the form of ohmic losses, n is the refractive index of the embedding medium, ε0 and µ0 are the permittivity and permeability of F | is the amplitude of the incident electric free space, and |E inc field. Similarly, the scattering cross section is the integral of the far field component of the outgoing electromagnetic energy flux over an arbitrary boundary surrounding the particle. The result is normalized by the power density of the incident field

Cscat )

∫ |FE far|2dΩ |F E inc | 2

(2)

Figure 1. Calculated ensemble average extinction (blue line), absorption (red line), and scattering (black line) spectra: (a) Au/SiO2 nanoshells ([r1, r2] ) [62, 77] nm) and (b) Au/Au2S nanoshells ([r1, r2] ) [21, 25] nm) in water, calculated by using Mie theory. Since these particles are spherically symmetric, the polarization of incoming light has no effect on the spectra. (c) Ensemble of randomly oriented nanorods ([l, d] ) [44, 13] nm) in aqueous solution calculated by using FEM. These can be obtained by simulating a particle oriented so that the incoming electric field projects equally onto all three axes (inset).

In eq 2, F E far is the far field component of the outgoing wave, calculated by using the Stratton-Chu formula. Details of the parameters used for our FEM model are similar to those used by Knight et al.14 For nanorods, the optical response of the nanoparticles depends on their orientation relative to the polarization of incident light. The optical response of a nanorod suspension in an aqueous medium is essentially an ensemble average over the random orientations of the nanorods. Fortunately, it is possible to model any particle orientation knowing the spectral response of only two key orientations: that for light polarized along the longitudinal axis of the nanorod and that for the

cross sections are most straightforwardly calculated by using Mie theory. The effective cross sections of the two nanoshell types in an aqueous medium (n ) 1.33) are shown in parts a and b of Figure 1. The size of the two nanoshell species was estimated by adjusting the core and shell radii to minimize the difference between Mie calculations and spectrophotometric measurements. For Au/SiO2 nanoshells, we found [r1, r2] ) [62, 77] nm and for Au/Au2S shells [r1, r2] ) [21, 25] nm. These values are in agreement with particle size statistics from scanning electron microscopy (SEM) and transmission electron microscopy (TEM) (Figure 2). Unlike nanorods, the spherical symmetry of nanoshells makes their spectrum insensitive to the polarization of incident light, so the plasmon mode will be excited equally in all particles in solution. From Mie calculations, we find that the Au/SiO2 nanoshells are predominantly scattering and that the Au/Au2S nanoshells are highly absorbing. However, the large physical size of the Au/SiO2 nanoshells makes the actual absorption cross section an order of magnitude higher than that of the other two particle species considered in this study. The finite element method was used to calculate the absorption and scattering cross sections of Au nanorods (Figure 1c), again in aqueous medium (n ) 1.33). The rods were modeled as cylinders with hemispherical end caps, as is consistent with other reported studies,13 using average dimensions ([l, d] ) [44, 13] nm) based on statistics from TEM measurements. The absorption cross section is calculated by integrating the resistive heating over the volume of the particle and dividing by the incident power density, as in eq 1

Figure 2. Images of particles used for photothermal transduction efficiency measurements. Variations in size and shape can mediate extremely absorbing or scattering particles. (a) SEM image of Au/SiO2 nanoshells. (b) TEM image of Au/Au2S nanoshells. (c) TEM image of nanorods.

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perpendicular polarization (see the Supporting Information). Since a nanoparticle oriented so that the electric field vector of an incoming electromagnetic wave projected equally onto all three axes (the [111] direction) is equivalent to many randomly oriented particles (Figure SI1 in Supporting Information), we were able to efficiently calculate the average spectrum for randomly oriented nanorods in solution. Our model predicts the Au nanorod plasmon resonance maximum at a wavelength of 740 nm, slightly shorter than the resonance wavelength (∼780 nm) measured by UV/vis spectroscopy of the nanorod solution from which size statistics were derived. The difference may arise from a slight size selectivity bias in the deposition of the nanorod population onto the TEM grid15 or from variations in the population’s end-cap geometry resulting in significant deviations of the resonance from the hemispherical end-cap model.16,17 A representative TEM image of the nanorods (Figure 2c) reveals that a significant fraction of the nanoparticles are slightly dog-bone shaped. Regardless of the model’s prediction of resonance peak, it confirms that extinction by nanorods is primarily due to absorption of the light, as opposed to scattering. According to our calculations, the nanorods used in this study are expected to absorb 93% of the incident light. The dielectric function of bulk gold reported by Johnson and Christy18 was used for Au/SiO2 nanoshells, in accordance with previous single nanoparticle optical measurements and analysis.19 For the smaller Au/Au2S nanoshells, the finite mean free path of electrons was taken into account in a modified dielectric function for Au.20 The calculated cross section of Au/Au2S nanoshells agrees well with the experimentally obtained spectra when this modification is included. Although surface scattering also affects the plasmon line width of nanorods,21 inhomogeneous broadening of the line shape of nanorods in solution is far greater than the anticipated effect of surface scattering on the line shape, and this contribution to the line broadening was neglected. Particle Fabrication. Au/SiO2 nanoshells were fabricated as previously described.22 Briefly, 120-nm diameter silica nanoparticles were obtained (Precision Colloids, Inc.) and suspended in ethanol. The particle surface was then terminated with amine groups by reaction with 3-aminopropyltriethoxysilane (Gelest). Very small gold colloid (1-3 nm diameter) was grown via the method of Duff et al.23 This colloid was aged for 4-14 days at 6-8 °C. The aminated silica particles were then added to the gold colloid suspension. Gold colloid adsorbs to the amine groups on the silica surface resulting in a silica nanoparticle covered with islands of gold colloid. Au/SiO2 nanoshells were then grown by reacting HAuCl4 (Sigma-Aldrich) with the silica-colloid particles in the presence of formaldehyde. Nanoshell surfaces were coated with PEG by adding 1 mM PEG-SH (Lysan Technologies, LLC) to the nanoshell solution overnight followed by diafiltration with a solution of trehalose (10% w/v) to remove residual PEG-SH from the nanoshell formulation. To make Au/Au2S nanoshells,24 a solution of Na2S2O3 (1.5 mM) was added to 2 mM HAuCl4. The resulting mixture was stirred for 30 min. The particles obtained were PEGylated by the addition of PEG-SH with stirring overnight. Excess PEGSH was removed via centrifugation and redispersion into a solution of trehalose (10% w/v). Thiolated PEG is a universally used coating of gold nanoparticles for in vivo applications: when absent or for cases of partial PEG coverage, unwanted protein aggregation may be induced by adsorbed and misfolded proteins

Cole et al. adhering to the available gold nanoparticle surface at physiological pH.25 Nanorods were synthesized by using the method developed by Jana et al.,26 with minor changes. In brief, gold seed particles were prepared by adding 250 µL of 10 mM HAuCl4 · 3H2O to 7.5 mL of 100 mM cetyltrimethylammonium bromide (CTAB) with brief, gentle mixing. A 600 µL sample of freshly prepared, ice-cold 10 mM NaBH4 solution was added, followed by mixing for 2 min. The nanorod growth solution was prepared by adding 40 mL of 100 mM CTAB, 1.7 mL of 10 mM HAuCl4 · 3H2O, and 250 µL of 10 mM AgNO3 followed by 270 µL of 100 mM ascorbic acid. To initiate nanorod growth, 840 µL of the seed solution was added to the growth solution, which was then mixed gently and left still for 40 min. Excess reactants were removed by centrifugation and resuspension in deionized (DI) water. The nanorods were PEGylated by the addition of 1 mM thiol terminated methoxypoly(ethylene glycol) mPEG-SH, and then the solution was left to stir overnight. The final PEGylated rod solution was cleaned by diafiltration of the solution into DI H2O. After cleaning, the particles were transferred via diafiltration into a 10% (w/v) solution of trehalose. Photothermal Conversion Efficiency Measurements. To find the photothermal transduction efficiency of our three types of nanoparticles, we measured the temperature of the nanoparticle solution as a function of time while it was heated with infrared laser irradiation, reached equilibrium, and subsequently cooled to ambient temperature. Following Roper et al.,27 the following energy balance equation can be used to describe this process

∑ miCp,i dT dt

) QI + Q0 + Qext

(3)

i

where m and Cp are the mass and heat capacity of each component of the sample cell, T is the sample cell temperature, QI is the energy input by nanoparticles, Q0 is the baseline energy input by the sample cell, and Qext is the outgoing energy. A model that is linear with temperature for the outgoing thermal energy is used, resulting in

∑ miCp,i dT dt

) hA(T - Tamb)

(4)

i

when there is no laser source incident on the sample. Here Tamb is the ambient temperature, A is the surface area of the sample cell, and h is the heat transfer coefficient. Following this model, the cooling portion of the thermal cycle has an exponential time dependence. Similarly, the heating portion of the cycle also has an exponential time dependence because both QI and Q0 are time independent. By finding the best exponential fit to the temperature data, we determine the characteristic thermal time constant for the system. The heat transfer coefficient of the sample cell is inversely proportional to the time constant

h)

∑ miCp,i i

τA

(5)

and this value should be the same regardless of whether it is calculated by using the heating or the cooling data. Once the heat transfer coefficient is known, it can be used to calculate

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Figure 3. Apparatus for measuring photothermal transduction efficiency: (a) 815-nm diode laser; (b) vacuum chamber held below 1 Torr; (c) aperture; (d) sample cell sealed with paraffin wax and epoxy; (e) T-type thermocouple; (f) Teflon-coated magnetic stir bar to eliminate temperature gradients in the cell.

the amount of heat energy accumulated in or lost from the sample cell, given the current temperature inside. When the sample cell reaches an equilibrium temperature, the power flowing into the sample cell is equivalent to the power outflow

QI + Q0 ) hA(Tmax - Tamb)

(6)

where Tmax is the equilibrium temperature. Therefore, the maximum temperature achieved by the cell is directly related to the power absorbed by the particles inside. The photothermal transduction efficiency is defined as the ratio of photothermal power transduced by the nanoparticles to the incident optical power

η)

hA(Tmax - Tamb) - Q0 I(1 - 10-Aλ)

Figure 4. Experimental data used to calculate photothermal transduction efficiency of nanorods and nanoshells in aqueous solution. (Left) Temperature change of representative sample cells as a function of time with exponential fits of heating (red lines) and cooling (blue lines). The time constant of the exponential fit allows calculation of the heat transfer coefficient of the sample cell and the photothermal transduction efficiency of the particles within. (Right) UV/vis absorbance spectra of solutions used, including (a) Au/SiO2 nanoshells, (b) Au/Au2S nanoshells, and (c) nanorods, shown with the laser line used to heat the particles (815 nm, red line).

(7)

where I is the power of the incident laser radiation after attenuation by any elements in the optical path and Aλ is the optical density of the sample solution at the laser wavelength. A schematic of the apparatus used to measure the photothermal transduction efficiency is depicted in Figure 3. The nanoparticle solution is contained in a sealed cuvette with a magnetic stir bar and a T-type thermocouple probe inside. The sample is irradiated with an 815 nm diode-laser (Optopower Corp., Model No. OPE-BO15-815-FCPS) through a 32 mm2 aperture. The entire cuvette is contained in a vacuum chamber held below 1 Torr to minimize sample cooling pathways through the surrounding atmosphere. The cuvette is sealed by a layer of paraffin wax to prevent nanoparticle aggregation followed by a layer of epoxy. Further details of sample construction are included in the Supporting Information. Only two cooling pathways remain: conduction through the thermocouple and blackbody radiation. Even though net energy loss through blackbody radiation has a quartic temperature dependence, the error resulting from our linear model for outgoing energy is negligible for the small temperature changes in our system. III. Results and Discussion Representative curves showing the photothermal temperature change of the sample cell and its contents for our three nanoparticle types shown are in Figure 4. Detailed experimental values associated with the data in Figure 4 can be found in the Supporting Information. The optical density of the samples was adjusted to be equivalent at the laser wavelength of 815 nm. Maintaining a constant optical density required widely varying nanoparticle concentrations because of the dramatic difference in the effective cross sections of the nanoparticles. We used an

Figure 5. Comparison of heating by nanoparticles. (a) Photothermal transduction efficiency of nanoshells and nanorods, calculated by eq 7 and averaged over several runs. (b) Photothermal transduction cross section (black bar) and absorption cross section (red bar) of nanoshells and nanorods.

approximately 3 pM solution of Au/SiO2 nanoshells, relative to approximately 100 and 300 pM for nanorods and Au/Au2S nanoshells, respectively. The observed temperature change follows a trend in qualitative agreement with predictions based on electromagnetic calculations alone, with Au/SiO2 nanoshells showing the smallest increase and Au/Au2S shells and nanorods showing somewhat larger temperature changes. The photothermal transduction efficiencies, calculated with eq 7 and averaged over several runs, show that nanorods have the highest efficiency, but the advantage over Au/Au2S nanoshells is not statistically significant (Figure 5a). On the other hand, when comparing strictly on the basis of how much light energy a single particle is expected to convert to heat, the photothermal transduction cross section of Au/SiO2 nanoshells is overwhelmingly higher than either of the other particle types (Figure 5b). We calculate the photothermal transduction cross section by multiplying the empirical efficiency of the particle by the theoretical extinction cross section. Despite expectations based on the calculated absorption efficiencies, the nanorod photothermal transduction efficiency is only about twice as large as the efficiency obtained for Au/ SiO2 nanoshells. The difference between the absorption and photothermal transduction efficiencies may seem surprising at first glance. Low intensity white light experiments using photoacoustic techniques28 or an integrating sphere29 to isolate absorption from extinction show good agreement with Mie theory predictions. However, closer analysis of their experimental technique reveals that the current measurement is not probing the same regime as those studies for two reasons. First, the particles used in this experiment are different. We are using Au nanoshells and Au nanorods instead of Ag colloid. With regard to nanoshells in particular, it is known that an asymmetric

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distribution of metal around the core, such as a dielectric core offset (nanoeggs30), can cause the particle to morph from predominantly scattering to predominantly absorbing.14 Other geometric imperfections, such as surface roughness, may also contribute to a particle’s tendency to absorb more than predicted by Mie theory.12,31 Second, in contrast to white light sources, laser illumination can deliver significantly more power to the particles. At the extreme, pump/probe experiments can deliver enough power to induce phase changes and particle reshaping.32-34 The intermediate power levels used in this experiment possibly caused local temperature increases sufficient to alter the optical environment of the nanoparticles.35 The temperature dependence of the solution’s refractive index could be responsible for a resonance shift by the particles, particularly if the local temperature were high enough to permit boiling. Water’s refractive index decreases gradually before it discontinuously jumps to n ) 1 at the boiling point.36,37 Nanorods in particular would be sensitive to this effect because of their narrow line width. Their plasmon peak need not shift very far before it no longer overlaps the laser line at all. Furthermore, nanoscale pockets of steam surrounding the nanoparticles38 may act as Rayleigh scattering centers not accounted for by the present theory. This hypothesis is consistent with the observation by Roper et al. that mechanically chopping the laser beam results in higher photothermal transduction efficiencies.27 The reduced duty cycle allows adequate time for any hot spots around the particles to dissipate. Unfortunately, it is extremely difficult to pinpoint the surface temperature of the particles because it depends on the thermal conductance of the particle/solvent interface. Reported values range over 2 orders of magnitude depending on particle surface chemistry, thermal properties of the embedding medium, and the rate at which energy is delivered to the nanoparticles.39-41 Further study is indicated in order to confirm these effects and find their relative magnitudes. IV. Conclusions The optimal nanoparticle species to use for heating applications ultimately depends on the specifics of the application in mind. While small nanoparticles such as nanorods and Au/Au2S nanoshells provide the highest transduction efficiencies, larger particles such as Au/SiO2 shells can satisfy given heating requirements with fewer particles. The substantial scattering cross section of Au/SiO2 nanoshells also makes them ideal for applications that benefit from simultaneous image enhancement. These measurements probe a regime of photothermal heating where electromagnetic calculations alone may not fully capture all the physics necessary to understand the system. Several hypotheses are put forward to explain the discrepancy between the electromagnetic calculations and the measured photothermal heating. Understanding the benefits or drawbacks of the large and increasing plurality of nanoparticles available for photothermal applications adds versatility to our ability to utilize these unique nano- and mesostructures well in other future applications. Acknowledgment. The authors thank NASA’s Graduate Student Researchers Program (Grant No. NNX07AO45H) for funding this work. We also appreciate the efforts of Rizia Bardhan and Felicia Tam, who obtained some of the TEM images used in this work. Supporting Information Available: Tabulated values of experimental parameters associated with the data shown in Figure 4; derivation of absorption and scattering spectra for ensemble of randomly oriented nanorods; a figure demonstrating

Cole et al. the combination of basis spectra to find the spectrum for randomly oriented nanorod; detailed description of sample preparation. This material is available free of charge via the Internet at http://pubs.acs.org. References and Notes (1) Liao, H.; Nehl, C. L.; Hafner, J. H. Nanomedicine 2006, 1, 201. (2) Sperling, R. A.; Gil, P. R.; Zhang, F.; Zanella, M.; Parak, W. J. Chem. Soc. ReV. 2008, 37, 1745. (3) West, J. L.; Halas, N. J. Annu. ReV. Biomed. Eng. 2003, 5, 285. (4) Vaia, R. A.; Baur, J. Science 2008, 319, 420. (5) MacDonald, K. F.; Samson, Z. L.; Stockman, M. I.; Zheludev, N. I. Ultrafast Active Plasmonics: Transmission and Control of Femtosecond Plasmon Signals, 2008, arXiv:0807.2542v1 [physics.optics]. (6) Nikolajsen, T.; Leosson, K.; Bozhevolnyi, S. I. Opt. Commun. 2005, 244, 455. (7) Dickerson, E. B.; Dreaden, E. C.; Huang, X.; El-Sayed, I. H.; Chu, H.; Pushpanketh, S.; McDonald, J. F.; El-Sayed, M. A. Cancer Lett. 2008, 269, 57. (8) Hirsch, L. R.; Stafford, R. J.; Bankson, J. A.; Sershen, S. R.; Rivera, B.; Price, R. E.; Hazle, J. D.; Halas, N. J.; West, J. L. Proc. Natl. Acad. Sci. U.S.A. 2003, 100, 13549. (9) Huang, X.; Jain, P. K.; El-Sayed, I. H.; El-Sayed, M. A. Lasers Med. Sci. 2008, 23, 217. (10) Loo, C.; Lowery, A.; Halas, N.; West, J.; Drezek, R. Nano Lett. 2005, 5, 709. (11) Hao, F.; Nehl, C. L.; Hafner, J. H.; Nordlander, P. Nano Lett. 2007, 7, 729. (12) Wang, H.; Goodrich, G. P.; Tam, F.; Oubre, C.; Nordlander, P.; Halas, N. J. J. Phys. Chem. B 2005, 109, 11083. (13) Jain, P. K.; Lee, K. S.; El-Sayed, I. H.; El-Sayed, M. A. J. Phys. Chem. B 2006, 110, 7238. (14) Knight, M. W.; Halas, N. J. New J. Phys. 2008, 10, 105006. (15) Eustis, S.; El-Sayed, M. A. J. Appl. Phys. 2006, 100, 044324. (16) Prescott, S. W.; Mulvaney, P. J. Appl. Phys. 2006, 99, 123504. (17) Xu, X.; Cortie, M. B. AdV. Funct. Mater. 2006, 16, 2170. (18) Johnson, P. B.; Christy, R. W. Phys. ReV. B 1972, 6, 4370. (19) Nehl, C. L.; Grady, N. K.; Goodrich, G. P.; Tam, F.; Halas, N. J.; Hafner, J. H. Nano Lett. 2004, 4, 2355. (20) Averitt, R. D.; Westcott, S. L.; Halas, N. J. J. Opt. Soc. Am. B 1999, 16, 1824. (21) Novo, C.; Gomez, D.; Perez-Juste, J.; Zhang, Z. Y.; Petrova, H.; Reismann, M.; Mulvaney, P.; Hartland, G. V. Phys. Chem. Chem. Phys. 2006, 8, 3540. (22) Oldenburg, S. J.; Westcott, S. L.; Averitt, R. D.; Halas, N. J. J. Chem. Phys. 1999, 111, 4729. (23) Duff, D. G.; Baiker, A.; Edwards, P. P. Langmuir 1993, 9, 2301. (24) Averitt, R. D.; Sarkar, D.; Halas, N. J. Phys. ReV. Lett. 1997, 78, 4217. (25) Zhang, D.; Neumann, O.; Wang, H.; Yuwono, V. M.; Barhoumi, A.; Perham, M.; Hartgerink, J. D.; Wittung-Stafshede, P.; Halas, N. J. Nano Lett. 2009, 9, 666. (26) Jana, N. R.; Gearheart, L.; Murphy, C. J. J. Phys. Chem. B 2001, 105, 4065. (27) Roper, D. K.; Ahn, W.; Hoepfner, M. J. Phys. Chem. C 2007, 111, 3636. (28) Kreibig, U.; Schmitz, B.; Breuer, H. D. Phys. ReV. B 1987, 36, 5027. (29) Evanoff, D. D., Jr.; Chumanov, G. J. Phys. Chem. B 2004, 108, 13957. (30) Wu, Y.; Nordlander, P. J. Chem. Phys. 2006, 125, 124708. (31) Oubre, C.; Nordlander, P. J. Phys. Chem. B 2005, 109, 10042. (32) Link, S.; El-Sayed, M. A. Annu. ReV. Phys. Chem. 2003, 54, 331. (33) Plech, A.; Kotaidis, V.; Gre´sillon, S.; Dahmen, C.; von Plessen, G. Phys. ReV. B 2004, 70, 195423. (34) Aguirre, C. M.; Moran, C. E.; Young, J. F.; Halas, N. J. J. Phys. Chem. B 2004, 108, 7040. (35) Brusnichkin, A. V.; Nedosekin, D. A.; Proskurnin, M. A.; Zharov, V. P. Appl. Spectrosc. 2007, 61, 1191. (36) Schiebener, P.; Straub, J.; Sengers, J. M. H. L.; Gallagher, J. S. J. Phys. Chem. Ref. Data 1990, 19, 677. (37) Schiebener, P.; Straub, J.; Sengers, J. M. H. L.; Gallagher, J. S. J. Phys. Chem. Ref. Data 1990, 19, 1617. (38) Egerev, S. V.; Oraevsky, A. A. J. Phys. IV 2006, 137, 273. (39) Richardson, H. H.; Hickman, Z. N.; Govorov, A. O.; Thomas, A. C.; Zhang, W.; Kordesch, M. E. Nano Lett. 2006, 6, 783. (40) Hu, M.; Hartland, G. V. J. Phys. Chem. B 2002, 106, 7029. (41) Wilson, O. M.; Hu, X.; Cahill, D. G.; Braun, P. V. Phys. ReV. B 2002, 66, 224301.

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