Cationic Surfactant-Induced Formation of Uniform Gold Nanoparticle

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Cationic Surfactant-Induced Formation of Uniform Gold Nanoparticle Clusters with High Efficiency of Photothermal Conversion under Near-Infrared Irradiation Lunjakorn Amornkitbamrung,† Jeonghun Kim,† Yeonggon Roh,† Sang Hun Chun,† Ji Soo Yuk,† Seung Won Shin,† Byung-Woo Kim,† Byung-Keun Oh,§ and Soong Ho Um*,†,‡ †

School of Chemical Engineering and ‡SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 16419, South Korea § Department of Chemical and Biomolecular Engineering, Sogang University, 35, Baekbeom-ro, Mapo-gu, Seoul 121-742, South Korea S Supporting Information *

ABSTRACT: A novel and simple method for the fabrication of gold nanoparticle (AuNP) clusters was introduced for use as an efficient near-infrared (NIR) photothermal agent. Cationic surfactants were employed to assemble AuNPs into clusters, during which polyvinylpyrrolidone (PVP) was used to stabilize the AuNP clusters. Through this manner, AuNP clusters with a uniform shape and a narrow size distribution (55.4 ± 5.0 nm by electron microscope) were successfully obtained. A mechanism for the formation of AuNP clusters was studied and proposed. Electrostatic interactions between AuNPs and cationic surfactants, hydrophobic interactions between hydrocarbon chains of cationic surfactants, and repulsive steric interactions of PVP were found to play an important role with regard to the formation mechanism. Photothermal effect in the NIR range of the AuNP clusters was demonstrated; results presented a highly efficient photothermal conversion (with a maximum η of 65%) of the AuNP clusters. The clusters could be easily coated by a silica layer, enabling their biocompatibility and colloidal stability in physiological fluids. The easy-to-fabricate AuNP clusters showed high potential of use as an NIR photothermal agent for cancer therapy.

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INTRODUCTION The unique surface plasmon resonance (SPR) of gold (Au) nanomaterials presents multiple modalities for biological and medical applications. With regard to photothermal cancer therapy, Au nanomaterials have been extensively researched and utilized as photothermal agents within the last decade. In particular, Au nanomaterials, which absorb near-infrared (NIR) light, have attracted considerable attention because NIR light (650−900 nm) can deeply penetrate biological tissue (as it is least absorbed by hemoglobin and water, compared to visible and infrared light).1 When NIR-absorbing Au nanomaterials are located within cancer cells, the absorbed photon energy can be converted into heat, initiating local hyperthermia and killing damaged cells. Thus, noninvasive photothermal cancer therapy can be performed in this manner.1 The NIR absorption characteristics of Au nanomaterials can be obtained by adjusting their size and shape during synthesis. Au nanorods are the most well-known and commonly used nanomaterials as they possess a tunable SPR band that is © XXXX American Chemical Society

adjustable from the visible to NIR range through variations in the material aspect ratio.2 Au nanoshells are also used and have become attractive NIR photothermal agents because of their strong absorption in the NIR region.3 Apart from adjustments to the size and shape of nanomaterials, NIR absorption properties can also be obtained by clustering spherical Au nanoparticles (AuNPs). It has been found that AuNP clusters on cell surfaces4 or within the cytosol,5,6 can shift the absorption properties from the visible to NIR spectrum. Assembled AuNP structures are efficient for photothermal cancer therapy because of their collective effects.7 However, the size and morphology of AuNP clusters obtained in this manner are not easy to control. The supramolecular assembly of AuNPs with organic ligands8−11 and control over the aggregation of AuNPs stabilized by polymers has thus been Received: November 1, 2017 Revised: December 30, 2017

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DOI: 10.1021/acs.langmuir.7b03778 Langmuir XXXX, XXX, XXX−XXX

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Figure 1. (a) UV−vis spectrum, (b,c) low- and high-magnification TEM images, (d) hydrodynamic diameter, and (e) zeta potential of the AuNP clusters compared to that of isolated AuNPs.

developed.12−14 These strategies have also been applied for clustering many kinds of inorganic nanoparticles.15 Recently, a new AuNP clustering method has been proposed by loading AuNPs into larger polymeric nanoparticles.16 The application of AuNP clusters as efficient photothermal agents for cancer therapy with a NIR laser has been continually demonstrated.16−18 Herein, a novel and simple method for the fabrication of AuNP clusters was introduced for use as an efficient NIR photothermal agent. The advantage of NP clusters over other nanostructures can be attributed to the simplicity of their fabrication and control. The fabrication of other NIR-active Au nanostructures such as nanorods, nanoshells, and nanocages has been shown to be complicated and time-consuming as finecontrol over crystal growth steps is mandatory to obtain such nanostructures. This requirement was not necessary to prepare AuNPs in this study. To fabricate AuNP clusters, cationic surfactants were employed to assemble AuNPs. The aggregation of AuNPs induced by cationic surfactants has been studied previously for a different purpose. In that case, AuNPs were employed for the colorimetric detection of cationic surfactants in the environment.19 The mechanism of AuNP aggregation was proposed to be induction by hydrophobic interactions between the hydrocarbon chains of cationic surfactants. This allowed for the detection of cationic surfactants because of a color change of AuNP dispersion as the result of aggregation. Instead of taking advantage of AuNPs for the detection of cationic surfactants, hydrophobic interactions between cationic surfactants were employed for the fabrication of AuNP clusters. A polymer, polyvinylpyrrolidone (PVP), was used to prevent the assembled AuNPs from aggregating. The role of PVP was to act as a capping agent to stabilize the assembled AuNPs through repulsive steric interactions.20 In this manner, AuNP clusters were successfully obtained with a uniform shape and a narrow size distribution. Photothermal effect within the NIR range of the AuNP clusters was demonstrated, revealing a highly efficient photothermal conversion of the AuNP clusters. The clusters could be easily

coated by a silica layer, enabling their biocompatibility and colloidal stability in physiological fluids. The easy-to-fabricate AuNP clusters showed high potential of use as an NIR photothermal agent for cancer therapy.

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EXPERIMENTAL SECTION

Materials. Tetrachloroauric acid trihydrate (HAuCl4·3H2O, 99.9%), trisodium citrate dihydrate (99%), dodecyltrimethylammonium bromide (DTAB, 98%), polyvinylpyrrolidone (PVP, Mw ≈ 55 000), ethylene glycol (EG, 99.8%), hexadecyltrimethylammonium bromide (CTAB, 99%), tetramethylammonium bromide (TMAB, 98%), sodium chloride (NaCl, 99%), ethanol (99%), ammonium hydroxide (28−30% NH3 basis), and tetraethyl orthosilicate (TEOS, 99%) were obtained from Sigma-Aldrich. All chemical were used as received without further purification. Deionized water (18.2 MΩ/cm) was used as a solvent. Synthesis of AuNPs. AuNPs were synthesized according to the standard sodium citrate reduction method.21 First, 100 mL of an aqueous HAuCl4 solution (1 mM) was heated to 100 °C under stirring. Then, 10 mL of an aqueous trisodium citrate dehydrate solution (38.8 mM) was added to the HAuCl4 solution. The solution mixture was stirred at 100 °C for 15 min prior to cooling to room temperature. A red-wine colored AuNP dispersion was obtained with a concentration of 12 nM. The AuNP concentration was calculated from its UV−vis spectrum using Haiss’s equation.22 Synthesis of AuNP Clusters. AuNP clusters were synthesized at room temperature (25 °C) using AuNPs as a precursor material. In a typical synthesis, 1 mL of an aqueous DTAB solution (20 mg/mL) was swiftly injected (24 mL/min) into 1 mL of an aqueous AuNP dispersion (12 nM). The solution mixture was placed in a vortex for 5 s and swiftly injected into 5 mL of a PVP/EG solution (2 mM) while stirring at 700 rpm. The solution mixture was continuously stirred for 30 min at room temperature. The resulting AuNP clusters were washed twice via centrifugation at 15 000g for 20 min using ethanol as a solvent and were finally redispersed in 1 mL deionized water. Characterization. The optical property of the AuNP clusters was investigated via UV−vis spectroscopy. UV−vis spectra were collected with a SpectraMax M5 microplate reader (Molecular Devices, Sunnyvale, CA, USA). A disposable cuvette with an optical path length of 10 mm was employed as a sample holder. All UV−vis spectra were referenced to deionized water. The morphology of the AuNP B


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Langmuir clusters was analyzed using transmission electron microscopy (TEM, JEOL JEM-3010) operating at 120 kV. Samples were prepared by dropping 10 μL of dispersion (sonicated for 5 min) on 200 mesh carbon-coated copper grids, followed by drying at room temperature. The hydrodynamic diameter and zeta potential of the AuNP clusters were determined using a Malvern Zetasizer Nano ZS90. The chemical composition of the AuNP clusters was analyzed via Fourier transform infrared (FT-IR) spectroscopy. FT-IR spectra were recorded using a Bruker IFS-66/S FT-IR spectrometer at a scan range of 4000−750 cm−1. A total of 32 scans were performed with a resolution of 2 cm−1. Photothermal Effect Experiment. Photothermal effect of the AuNP clusters was investigated using an 808 nm NIR laser. Concentrations of aqueous AuNP cluster dispersions (1 mL) were varied from 0.5 to 2.0 according to their optical density (OD) at 450 nm. Dispersions were irradiated for 10 min with a laser power of 500 mW (2.5 W/cm2, measured by a power meter). The temperature change was noninvasively recorded every 10 s using an IR thermometer with an accuracy of ±0.1 °C; measurements were repeated three times to ensure reproducibility. Silica Coating of AuNP Clusters. Silica coating of the AuNP clusters was carried out according to the simple sol−gel process.23 Right after the AuNP clusters were washed twice via centrifugation at 15 000g for 20 min using ethanol, the pellet was redispersed in 10 mL ethanol (the concentration of AuNP clusters was 8.3 ± 0.7 μg/mL measured by using a gravitational method.). Under stirring at 700 rpm, 1.5 mL of deionized water and 0.5 mL of ammonium hydroxide solution were added dropwise to the dispersion. TEOS (10 μL) was then injected and the mixture was kept stirring at room temperature for 30 min. The resulting silica-coated AuNP clusters were washed several times via centrifugation at 15 000g for 20 min using ethanol as a solvent and were finally redispersed in 1 mL deionized water.

analysis because of a hydrated citrate layer around the nanoparticles. The zeta potential of the AuNP clusters was measured to be −10.5 ± 1.5 mV, which was moderately lower than the zeta potential of isolated AuNPs (−28.5 ± 3.0 mV), Figure 1e. This implied the existence of a different type of surface stabilization between the AuNP clusters and isolated AuNPs. The FT-IR spectroscopy results supported this incidence. The FT-IR spectrum of AuNPs (Figure S2a) revealed two strong absorption peaks at 1400 and 1590 cm−1, corresponding to the asymmetric and symmetric stretching vibrations of COO−, respectively. The FT-IR spectrum also revealed a broad absorption peak centered at 3500 cm−1, corresponding to the stretching vibrations of O−H.25 These peaks implied that the isolated AuNPs were stabilized by trisodium citrate. On the other hand, two strong absorption peaks at 1083 and 1900 cm−1 corresponding to stretching vibrations of C−N and C−H, respectively, were observed in the FT-IR spectrum of the AuNP clusters (Figure S2b).26 These observed peaks implied that the AuNP clusters were stabilized by PVP. Mechanism of AuNP Cluster Formation. A study with regard to the mechanism of AuNP cluster formation was performed and proposed. Cluster formation was divided into two steps. The first step involved the assembly of AuNPs induced by DTAB while the second step involved stabilization of the assembled AuNPs by PVP, leading to the formation of stable AuNP clusters. In the first step, DTAB, a cationic surfactant, became bound to the anionic AuNP surface through electrostatic interactions. The necessity of electrostatic interactions with regard to the assembly of AuNPs was previously discovered by Zheng et al., who reported that the assembly of citrate-capped AuNPs could not be achieved through the use of neutral or anionic surfactants.19 Shrivas et al. recently confirmed the existence of electrostatic interactions between the cationic surfactant and anionic AuNPs (tartratecapped).27 After the binding of DTAB to the AuNPs through electrostatic interactions, AuNP assembly was induced through hydrophobic interactions between the hydrocarbon chains of DTAB. A color-change of the dispersion from red to violet could already be noted when the AuNPs were assembled using DTAB (without injecting to PVP solution). The UV−vis spectrum of the assembled AuNPs showed a shift in the absorbance maximum to a longer wavelength of 530 nm with peak broadening (Figure S3). The hydrodynamic diameter of the assembled AuNPs was 29.6 ± 1.2 nm. The zeta potential of the assembled AuNPs was 21.2 ± 1.5 mV, implying that the assembled AuNPs were surface-stabilized by the cationic layer of DTAB. The necessity of hydrophobic interactions for the assembly of AuNPs was reported by Shrivas et al. showing that cationic metal ions (Na+ and Cu2+) could not induce the assembly of AuNPs.27 To confirm the presence of hydrophobic interactions, AuNP clusters were prepared with a longer hydrocarbon chain cationic surfactant (CTAB) instead of DTAB. As expected, AuNP assembly was observed by a color-change of the dispersion from red to violet. The UV−vis spectrum revealed a shift in the absorbance maximum from 520 nm for isolated AuNPs to a longer wavelength of 550 nm with peak broadening (Figure S4a). Interestingly, AuNP assembly could still be achieved with a short hydrocarbon chain cationic surfactant (TMAB) as a color-change of the dispersion from red to dark blue was detected. The UV−vis spectrum also revealed a shift

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RESULTS AND DISCUSSION Formation and Characteristic of AuNP Clusters. AuNP clusters were synthesized through an assembly of AuNPs. DTAB, a cationic surfactant, was employed to induce an aggregation of citrate-capped AuNPs into the clusters, which were subsequently stabilized with PVP. The change in optical property was observed upon the formation of AuNP clusters. The color of dispersion changed from red (AuNPs) to violet (AuNP clusters) as can be seen in the inset of Figure 1a. The incidence was supported via UV−vis spectroscopic analysis (Figure 1a). The UV−vis spectrum of AuNP dispersion revealed a maximum absorbance at 520 nm because of the surface plasmon resonance of isolated AuNPs. The formation of AuNP clusters involved the shift of the absorbance maximum to a longer wavelength of 540 nm, in addition to a peak broadening. These results could be attributed to the aggregation of AuNPs causing plasma mode coupling, resulting in a red shift and broadening of the longitudinal plasma resonance within the optical spectrum.24 Low- and high-magnification TEM images (Figure 1b,c) showed a spherical shape of the AuNP clusters with an average diameter of 55.4 ± 5.0 nm. The clusters were composed of spherical AuNPs with an average diameter of 12.1 ± 1.0 nm, which was comparable to the starting materials of citratecapped AuNPs (Figure S1). Through a dynamic light scattering (DLS) analysis, the hydrodynamic diameter of the AuNP clusters was 97.2 ± 1.4 nm with a low polydispersity index of 0.182 ± 0.007, Figure 1d. Compared to the diameter of AuNP clusters obtained via TEM analysis, a larger diameter was observed via DLS analysis because of the hydrated PVP layer around the clusters within the aqueous dispersion. Similar incidence could also be observed in the case of isolated AuNPs, which featured a reported diameter on DLS analysis (19.8 ± 0.2 nm, Figure 1d), which was larger than that obtained via TEM C


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Scheme 1. Mechanism of AuNP Cluster Formation through the Assembly of AuNPs Induced by Cationic Surfactants and PVP Polymer Stabilization

Figure 2. (a) UV−vis spectra and (b) hydrodynamic diameters of AuNP clusters synthesized with different concentrations of DTAB. (c) UV−vis spectra and (d) hydrodynamic diameters of AuNP clusters synthesized with different rates of DTAB injection. It should be noted that the other parameters were fixed according to the standard method of AuNP cluster synthesis (20 mg/mL of DTAB concentration, 24 mL/min of DTAB injection, 2 mM of PVP concentration, 25 °C of temperature, 700 rpm of stirring speed, 30 min of stirring time, 1 min of time before mixing).

in the absorbance maximum to a longer wavelength (540 nm) with peak broadening (Figure S4b). The hydrodynamic diameter of the AuNP clusters prepared using CTAB and TMAB was 177.7 ± 3.6 and 193.5 ± 12.1 nm, respectively. The results indicated that regardless of the number of carbons possessed by the cationic surfactant, hydrophobic interactions between the hydrocarbon chains of cationic surfactants played a primary role in the assembly of AuNPs. In the second step, DTAB-induced assembled AuNPs were transferred to a solution of PVP in EG to form stable AuNP clusters. PVP played an important role toward stabilizing the clusters because of steric hindrance effects. Without PVP (only EG), uniformly spherical and uniformly sized clusters were not obtained after washing (Figure S5). It should be noted that a massive aggregation of AuNPs was obtained when the DTABinduced assembled AuNPs were not subjected to PVP/EG or EG in the second step (Figure S6). Although it was clear that PVP played role as a stabilizer, there was a doubt on the driving force for the aggregation and growth of DTAB-induced assembled AuNPs into larger AuNP clusters. This was due to

the evidence that the average diameter of AuNP clusters (55.4 nm, from TEM analysis) was larger than the hydrodynamic diameter of DTAB-induced assembled AuNPs. It was speculated that EG used as a solvent of PVP solution was the driving force for the aggregation and growth of DTAB-induced assembled AuNPs into AuNP clusters. The effect of EG could be explained by its relative polarity, which is lower than water (the relative polarity of EG is 0.79). This could induce the aggregation and growth of the DTAB-induced assembled AuNPs as their surface was highly polar because of the DTAB attachment. To prove this hypothesis, an additional experiment was done by changing the solvent of PVP solution from EG to water, a solvent with a higher relative polarity (1.00). As presented in Figure S7, the UV−vis spectrum of AuNP clusters prepared by using a PVP solution (2 mM) in water showed a maximum absorbance at 527 nm. The peak was shifted to the shorter wavelength comparing to the UV−vis spectrum of AuNP clusters prepared by using the conventional PVP solution (2 mM) in EG. Moreover, it showed a much less peak broadening. These results implied that AuNPs were much D


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Figure 3. (a) UV−vis spectra and (b) hydrodynamic diameters of AuNP clusters synthesized with different concentrations of PVP. (c) UV−vis spectra and (d) hydrodynamic diameters of AuNP clusters synthesized at different temperatures. It should be noted that the other parameters were fixed according to the standard method of AuNP cluster synthesis (20 mg/mL of DTAB concentration, 24 mL/min of DTAB injection, 2 mM of PVP concentration, 25 °C of temperature, 700 rpm of stirring speed, 30 min of stirring time, 1 min of time before mixing).

less aggregated when water was used as the solvent instead of EG. As expected, there was no significant difference between UV−vis spectra of AuNP clusters prepared by using 0 and 2 mM PVP solution in water, indicating that PVP might not involve as a driving force for the aggregation and growth of DTAB-induced assembled AuNPs into AuNP cluster. In summary, the driving force for the aggregation and growth of DTAB-induced assembled AuNPs into AuNP clusters was proposed to be the low relative polarity of EG solvent, while PVP contributed as a stabilizer controlling the aggregation and growth of the assembled AuNPs. On the basis of this study, a mechanism of AuNP cluster formation was proposed in Scheme 1. Influence of Synthesis Parameters on the Formation of AuNP Clusters. A study was conducted to understand the influence of synthesis parameters on the formation of AuNP clusters. It should be noted that when each parameters were varied, the others were fixed according to the standard method of AuNP cluster synthesis (see Experimental Section). As shown in Scheme 1, the concentration of DTAB and the rate of its injection were expected to be vital in the first step of the formation mechanism and were selected for the study. The concentrations of DTAB were varied from 1 to 30 mg/mL. In Figure 2a, all UV−vis spectra of AuNP clusters synthesized with high concentrations of DTAB (10−30 mg/mL) showed absorbance maxima at 540 nm. However, a slight broadening of the peaks was observed when concentrations of DTAB were lower than 20 mg/mL. When concentrations of DTAB were lower than 10 mg/mL, UV−vis spectra of AuNP clusters became completely broad, indicating a large degree of aggregation. This was supported by a sudden increase of the hydrodynamic diameters as shown in Figure 2b. As an example, TEM images (Figure S8) showed a large aggregation of AuNP clusters synthesized with 1 mg/mL DTAB. The concentration of DTAB affected the size of AuNP clusters because of the

electrostatic repulsion. At a higher concentration of DTAB, the surface charge of DTAB-induced assembled AuNPs was highly positive because of the formation of a DTAB bilayer on their surface. Therefore, the assembled AuNPs were well-stabilized through the electrostatic repulsion, resulting in a less aggregation and formation of AuNP clusters with a smaller size. On the other hand, electrostatic stabilization of the assembled AuNPs was not sufficient at a lower concentration of DTAB, resulting in a large degree of aggregation and formation of AuNP clusters with a larger size. A previous study of Zheng et al. could be used to support this explanation.19 The rates of DTAB injection were varied from 1 to 24 mL/min. In Figure 2c, all UV−vis spectra of AuNP clusters synthesized with different rates of DTAB injection showed absorbance maxima at 540 nm. A gradual broadening of the peaks was observed as the rates of injection were decreased. Hydrodynamic diameters were gradually increased because of the decrease of injection rates (Figure 2d). On the basis of the results, a large aggregation of AuNP clusters was not pronounced. As an example, TEM images (Figure S9) showed a rather uniform size and shape of AuNP clusters synthesized with 1 mL/min of DTAB injection. The rate of DTAB injection influenced the size of AuNP clusters because of the rate of AuNP aggregation and supply of DTAB for electrostatic stabilization. Higher rates of DTAB injection induced a short period of AuNP aggregation and rapid stabilization of the assembled AuNPs, resulting in the formation of a smaller size AuNP clusters. At a lower rate of DTAB injection, a long period of AuNP aggregation as well as the slow supply of DTAB for stabilization allowed the assembled AuNPs to grow into a larger size AuNP clusters. Several parameters from the second step of the formation mechanism were selected for the study. The concentrations of PVP were varied from 0.1 to 2 mM. In Figure 3a, UV−vis spectra of AuNP clusters synthesized with different concentrations of PVP showed a gradual shift of absorbance maxima E


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Langmuir from 540 to 600 nm as the concentrations of PVP were decreased. A gradual broadening of the peaks was also observed. Hydrodynamic diameters were gradually increased because of the decrease of PVP concentrations (Figure 3b), indicating the formation of larger clusters. As an example, TEM images (Figure S10) showed large-sized (100 nm) AuNP clusters synthesized with 0.1 mM PVP. The concentration of PVP affected the size of AuNP clusters because of the steric hindrance effect. At a higher concentration of PVP, the aggregation of DTAB-induced assembled AuNPs was wellprevented because of the bumper effect of PVP adsorbed on their surface.28,29 The assembled AuNPs were then grown into AuNP clusters with a smaller size. The effect of temperature was not pronounced like other factors. In Figure 3c, UV−vis spectra of AuNP clusters synthesized at different temperatures showed a slight shift and broadening of absorbance maxima as the temperatures were increased. Hydrodynamic diameters were slightly increased because of the increase of temperatures (Figure 3d). TEM images in Figure S11 showed 50−60 nm AuNP clusters synthesized at 80 °C. The morphology was similar to that synthesized at 25 °C (Figure 1b,c). The temperature affected the size of AuNP clusters because of the aggregation kinetics through the random Brownian motion of particles and the collision frequency.30 At a higher temperature, the aggregation of DTAB-induced assembled AuNPs was promoted. The assembled AuNPs were then grown into AuNP clusters with a larger size. However, the degree of aggregation was not high because of the effect of PVP as a stabilizer. The effect of stirring speed (100, 200, 500, 700, and 1000 rpm), stirring time (10, 30, 60, 120, and 180 min), and time before mixing (1, 10, 30, and 60 min) was also studied. However, their influence on the optical property and hydrodynamic diameter of AuNP clusters was not significant. UV−vis spectra of AuNP clusters synthesized with these conditions were nearly overlapped, whereas their hydrodynamic diameters were in the same range of ±10 nm (data not shown). Optical Property of AuNP Clusters Controlled by Sodium Chloride. Optical property of the AuNP clusters could be controlled through the inclusion of NaCl during their synthesis. Different quantities of NaCl ranging from 2 to 3 mg were added to the AuNP dispersions while stirring at 700 rpm 5 s prior to the addition of DTAB. Different quantities of NaCl resulted in the formation of AuNP clusters with different optical properties. This was noticed by a gradual change in the dispersion color from violet to deep-blue as the quantities of NaCl were increased (inset of Figure 4a). This incidence was supported via UV−vis spectroscopic analysis (Figure 4a). UV− vis spectra of the AuNP clusters revealed a gradual shift in the absorbance maxima from 540 to 590 nm. Absorbance within the NIR region of 700−900 nm also successively increased. Variations in the optical property of the AuNP clusters could be attributed to the effects of NaCl-induced AuNP aggregation. Under high ionic strength conditions, electrostatic repulsion among AuNPs was diminished because of the screening of charges on the AuNP surface. The higher the ionic strength, the lower the stability of the AuNPs.31 This promoted AuNP aggregation, resulting in the formation of larger-sized AuNP clusters with altered optical properties. The formation of large AuNP clusters due to the effects of NaCl was confirmed by the DLS analysis results. As the quantities of NaCl increased from 0 to 3 mg, the hydrodynamic diameters of the AuNP clusters gradually increased from 97.2 ± 1.4 to 103.0 ± 2.0, 187.5 ± 3.3, 218.6 ± 3.0, 237.5 ± 3.3, and 255.8 ± 3.1 nm, respectively

Figure 4. (a) UV−vis spectra and (b) hydrodynamic diameters of the AuNP clusters synthesized with different quantities of NaCl. It should be noted that the other parameters were fixed according to the standard method of AuNP cluster synthesis (20 mg/mL of DTAB concentration, 24 mL/min of DTAB injection, 2 mM of PVP concentration, 25 °C of temperature, 700 rpm of stirring speed, 30 min of stirring time, 1 min of time before mixing).

(Figure 4b). As an example, TEM images of AuNP clusters synthesized with the inclusion of 2.5 mg NaCl were taken. The images (Figure S12) showed the AuNP clusters with an average diameter of 92.0 ± 22.9 nm. Apart from their larger diameter, they had a less uniformly spherical shape, compared to AuNP clusters synthesized without the inclusion of NaCl. It should be noted that the size obtained from the DLS analysis (218.6 ± 3.0) was larger than the one obtained from TEM analysis because of the hydrated PVP layer around the clusters within the aqueous dispersion. Photothermal Effect of AuNP Clusters. To demonstrate the potential application of the AuNP clusters as a photothermal agent, an experiment was performed using an 808 nm NIR laser. Concentrations of AuNP cluster dispersions were varied according to their OD at 450 nm. The progressive increase in temperature upon laser exposure was noninvasively monitored with an IR thermometer. AuNP clusters of 55 nm size (synthesized without the inclusion of NaCl) and AuNP clusters of 92 nm size (synthesized with the inclusion of 2.5 mg NaCl) were selected for the experiment. It should be noted that the sizes of clusters were obtained from the TEM analysis. As can be seen in Figure 5, the temperatures of the 55 and 92 nm AuNP cluster dispersions under irradiation increased in the range of 7.5−14.0 and 10.0−16.0 °C, respectively, within 10 min. On the other hand, the temperature of deionized water only increased by 2.5 °C. These results indicated that the AuNP clusters were efficient with regard to exhibiting the photothermal effect. The temperature increase as a function of time with an increase in the AuNP cluster concentrations was observed. As the concentrations of the 55 nm AuNP clusters increased from 0.5 OD to 1.0, 1.5, and 2.0, temperature F


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Figure 5. Concentration-dependent temperature profiles of (a) 55 and (b) 92 nm AuNP cluster dispersions in water irradiated by an 808 nm NIR laser.

Figure 6. (a) Temperature rising and decay curves of 55 and 92 nm AuNP cluster dispersions in water irradiated by an 808 nm NIR laser and (b) photothermal conversion efficiencies calculated from the curves.

increases of 7.5, 10.5, 12.5, and 14.0 °C were obtained, respectively (Figure 5a). With regard to the 92 nm AuNP clusters, temperature increases of 10.0, 12.5, 14.5, and 16.0 °C were obtained, respectively (Figure 5b). These results indicated that the photothermal effect of the AuNP clusters depended on their concentrations. The photothermal conversion efficiency (η) of the AuNP clusters was determined using a standard method following the Roper’s report.32−34 Briefly, the AuNP cluster dispersion was continuously irradiated by an 808 nm NIR laser with a power of 500 mW (2.5 W/cm2) until the temperature reached a plateau (at 660 s). The laser was then switched off while the temperature was monitored to determine the rate of heat transfer from the system (Figure 6a). The photothermal conversion efficiency was calculated using eq 1. η=

θ=

t = −τS ln(θ )

mDC D hS

(4)

As presented in Figure 6b, the calculated photothermal conversion efficiency of 92 nm AuNP clusters (65%) was higher than that of 55 nm AuNP clusters (57%). This could be attributed to the greater degree of light absorption within the NIR region for the larger clusters (Figure 4a). The photothermal conversion efficiency of AuNP clusters was comparable to that of the previous report of AuNP aggregates (52%) in the phosphate buffer saline solution.35 Moreover, it was higher than that of AuNSs (25−39%) and comparable to some cases of AuNRs (50−55%), suggesting the high photothermal conversion efficiency of AuNP clusters. However, it was still lower than a case of AuNRs, which a more than 90% of photothermal conversion efficiency in the NIR region was reported.36 Formation and Photothermal Effect of Silica-Coated AuNP Clusters. As the potential application of AuNP clusters was proposed to be photothermal agents for cancer therapy, biocompatibility and colloidal stability in physiological fluids of the clusters should be considered. Especially, the cationic surfactant (DTAB) used for the synthesis could be toxic for a biological use. Therefore, we demonstrated in this section that the clusters could be coated by a silica layer, to enable their biocompatibility and colloidal stability. It is well-known that silica coating provides biocompatibility and colloidal stability in physiological fluids to nanomaterials.23,37,38 Moreover, the silica

(1)

where h is the heat transfer coefficient, S is the surface area of the container, and Tmax and Tmin are the maximum and minimum temperature (room temperature), respectively, Q0 is the heat dissipated from light absorbed by the sample cell itself, and it was measured independently to be 7.9 mW using a polystyrene cuvette cell containing pure water without AuNP clusters, I is the incident laser power (500 mW), and A808nm is the absorbance of AuNP clusters at 808 nm. hS was obtained by measuring the drop rate of temperature after the laser was switched off and the value of hS was derived according to eqs 2 and 3. τS =

(3)

where τS is the sample system time constant, mD and CD are the mass and heat capacity of deionized water used as a solvent, respectively, and θ is the dimensionless parameter. The value of τS was calculated using the data from Figure S13 and eq 4.

hS(Tmax − Tmin) − Q 0 I(1 − 10−A808nm)

T − Tmin Tmax − Tmin

(2) G


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Figure 7. (a) UV−vis spectrum of silica-coated AuNP clusters compared to that of bare AuNP clusters, (b) TEM image of silica-coated AuNP clusters, and (c) temperature rising and decay curves of silica-coated 55 nm AuNP cluster dispersion in water irradiated by an 808 nm NIR laser.

clusters was demonstrated; results presented a highly efficient photothermal conversion (with a maximum η of 65%) of the AuNP clusters. The clusters could be easily coated by a silica layer, enabling their biocompatibility and colloidal stability in physiological fluids. For the further study, an application of materials for NIR photothermal treatment of cancer will be explored in vitro and in vivo.

layer enables the further surface functionalization, which is required for some biological applications. Silica coating of AuNP clusters was carried out by a simple sol−gel process.23 A change in optical property was observed after coating. In Figure 7a, UV−vis spectrum of silica-coated AuNP clusters showed a shift in the absorbance maximum to a longer wavelength of 550 nm, in addition to a peak broadening. The shift was according to an increase in the local refractive index around the clusters because of the silica layer.37,38 The colloidal stability of silicacoated AuNP clusters in water was measured and results showed that the silica-coated clusters were highly stable in water, in a similar way to the PVP-stabilized clusters (Figure S14). The TEM image (Figure 7b) showed that the thickness of silica layer was approximately 25 nm. The temperature rising and decay curves (Figure 7c) of silica-coated 55 nm AuNP cluster dispersion in water irradiated by an 808 nm NIR laser was determined and the photothermal conversion efficiency was calculated (the value of τS was calculated using the data from Figure S15) to be 65%, suggesting that the high photothermal conversion efficiency of AuNP clusters was retained after silica coating.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.langmuir.7b03778. TEM image and FT-IR spectra of AuNPs and AuNP clusters; UV−Vis spectra of AuNP clusters synthesized using various surfactants; low- and high-magnification TEM images of AuNP clusters under various conditions; and linear time data from the cooling period of AuNP cluster dispersion (PDF)

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AUTHOR INFORMATION

Corresponding Author

CONCLUSIONS In summary, AuNP clusters were fabricated using a novel and simple method. Cationic surfactants were employed to assemble the AuNPs into clusters, where the PVP polymer was used to stabilize the AuNP clusters. In this manner, AuNP clusters with a uniform shape and a narrow size distribution (55.4 ± 5.0 nm by TEM) were successfully obtained. The mechanism of AuNP cluster formation was studied and proposed. It was found that electrostatic interactions between AuNPs and cationic surfactants, hydrophobic interactions between the hydrocarbon chains of the cationic surfactants, and repulsive steric interactions of PVP played an important role with regard to the formation mechanism. Optical properties within the NIR range of the AuNP clusters could be controlled through the inclusion of NaCl during their synthesis. Photothermal effect in the NIR range of the AuNP

*E-mail: [email protected]. ORCID

Soong Ho Um: 0000-0002-2910-5629 Author Contributions

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (grant no. HI16C1984), H


Article

Langmuir

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by the Basic Science Research Programs through the National Research Foundation (NRF) funded by the Ministry of Science ICT and Future Planning (grant no. 2015R1A2A2A01007843), and by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (grant nos. 2016R1D1A1B03931270 and 2017R1D1A1B03027897).

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ABBREVIATIONS Au, gold; SPR, surface plasmon resonance; AuNP, gold nanoparticle; AuNRs, gold nanorods; AuNSs, gold nanoshells; NIR, near-infrared; DTAB, dodecyltrimethylammonium bromide; PVP, polyvinylpyrrolidone; CTAB, hexadecyltrimethylammonium bromide; TMAB, tetramethylammonium bromide; EG, ethylene glycol; TEM, transmission electron microscopy; DLS, dynamic light scattering; FT-IR, Fourier transform infrared; PDI, polydispersity index; OD, optical density

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Cationic Surfactant-Induced Formation of Uniform Gold Nanoparticle

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