Gold Nanoparticles-Decorated Silicon Nanowires as Highly Efficient

Letter pubs.acs.org/NanoLett

Gold Nanoparticles-Decorated Silicon Nanowires as Highly Efficient Near-Infrared Hyperthermia Agents for Cancer Cells Destruction Yuanyuan Su,1,2 Xinpan Wei,1 Fei Peng,1 Yiling Zhong,1 Yimei Lu,1 Shao Su,1 Tingting Xu,1,2 Shuit-Tong Lee,*,2 and Yao He*,1 1

Institute of Functional Nano and Soft Materials (FUNSOM) and Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou 215123, China 2 Center of Super-Diamond and Advanced Films (COSDAF) and Department of Physics and Materials Science, City University of Hong Kong, Hong Kong SAR, China S Supporting Information *

ABSTRACT: Near-infrared (NIR) hyperthermia agents are of current interest because they hold great promise as highly efficacious tools for cancer photothermal therapy. Although various agents have been reported, a practical NIR hyperthermia agent is yet unavailable. Here, we present the first demonstration that silicon nanomaterials-based NIR hyperthermia agent, that is, gold nanoparticles-decorated silicon nanowires (AuNPs@SiNWs), is capable of high-efficiency destruction of cancer cells. AuNPs@SiNWs are found to possess strong optical absorbance in the NIR spectral window, producing sufficient heat under NIR irradiation. AuNPs@SiNWs are explored as novel NIR hyperthermia agents for photothermal ablation of tumor cells. In particular, three different cancer cells treated with AuNPs@SiNWs were completely destructed within 3 min of NIR irradiation, demonstrating the exciting potential of AuNPs@SiNWs for NIR hyperthermia agents. KEYWORDS: Silicon nanowires, hyperthermia agent, cancer photothermal therapy, near-infrared, nanobioapplications

S

quantum dots (QDs)-decorated SiNWs feature remarkable antiphotobleaching property superbly suitable for long-term cellular imaging (e.g., SiNWs-labeled cells preserve stable and bright fluorescence during 90 min UV irradiation, whereas CdTe QDs rapidly diminish in fluorescence signals in 20 min observation under the same conditions).21 Those attractive properties strongly suggest SiNWs as a promising platform for the design of high-performance SiNWs-based nanohybrids with unique merits. On the other hand, nanomaterials-based hyperthermia agents have been intensively investigated for cancer cell destruction. The agents with strong NIR (700−1000 nm) absorbance, that is, NIR hyperthermia agents, are of particular interest since biological systems are transparent to NIR light. As a result, continuous NIR radiation can effectively cause cell death because of excessive local heating of the NIR hyperthermia agents in vitro. 22−24 In the past several years, gold nanostructures (e.g., gold nanorods and nanoshells)-based NIR hyperthermia agents have been reported for photothermal destruction of cancer cells. For instance, West et al. and Drezek et al. demonstrated gold nanoshells as highly efficient NIR

ilicon nanostructures (e.g., nanodots, nanowires, nanopillar, and so forth) have been extensively studied due to their many attractive properties, such as excellent electronic/ mechanical properties, convenient surface tailorability, and compatibility with conventional silicon technologies.1−6 Particularly, silicon nanowires (SiNWs) have drawn intensive attention for various promising applications ranging from electronics to biology.7−14 For biological applications, Lieber and co-workers fabricated SiNWs-based field-effect transistors for high-sensitivity biomolecular detection and stimulation of neuronal signal propagation.15 Yang and co-workers demonstrated interfacing of SiNWs with mammalian cells without any external force.16 Recently, SiNWs were employed as a bioimaging agent with intrinsic 3D spatial resolution, high photostability, and orientation information, providing new opportunities for cellular interaction studies.17 Wang et al. presented a SiNWs-based system for quantifying mechanical behavior of cells lines, revealing force information of cancer cells.18 Lee and co-workers designed SiNWs-based bio/ chemical sensors for detection of biological molecules and metal ions.13,19 In particular, recent studies demonstrate that silicon-based nanohybrids made of SiNWs decorated with nanoparticles (NPs) exhibit remarkable properties. For example, silver nanoparticles (AgNPs)-decorated SiNWs show ultrahigh surface-enhanced Raman scattering and antibacterial activity, much better than free AgNPs.13,19,20 Fluorescent © 2012 American Chemical Society

Received: November 29, 2011 Revised: February 28, 2012 Published: March 8, 2012 1845

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Figure 1. (a) SEM image and (b) TEM image, (c) size distribution, and (d) EDX pattern of the as-prepared AuNPs@SiNWs.

cm2). Significantly, cellular experiment demonstrates that the AuNPs@SiNWs, serving as high-performance NIR hyperthermia agents, are superbly efficacious for cancer cells destruction. SiNWs were prepared via a well-established HF-assisted etching method; afterward gold ions were readily reduced by Si−H bonds on SiNWs in 10 μg/mL) due to cytotoxicity of AuNPs.48,49 For instance, only ∼60% cell viability was observed when AuNPs@SiNWs concentration reached 60 μg/mL. In striking contrast, the KB cells retained >80% cell viability when cultured with 0.03−60 μg/mL PEG-AuNP@SiNWs. Moreover, PEG-AuNP@SiNWs of higher concentrations (∼300 μg/mL) only showed little cytotoxicity to KB cells in short-time incubation (e.g., 30 min, Supporting Information Figure S5). Significantly, like AuNPs@SiNWs, PEG-AuNP@SiNWs also feature large NIR photothermal effect, that is, a large ΔT of ∼40 °C was obtained for 150 μg/mL PEG-AuNP@SiNWs under 5 min irradiation (Figure 4b). Consequently, we investigated PEG-AuNPs@SiNWs of high NIR photothermal effect and favorable cytocompatibility for hyperthermia ablation of cancer cells. We evaluated in vitro photothermal ablation capacity of the PEG-AuNPs@SiNWs in a detailed way. KB cancer cells incubated with or without PEG-AuNPs@SiNWs (150 μg/ mL) were exposed to 808 nm laser of 2 W/cm2 for 3 min. After

Figure 2. (a) UV−vis-NIR spectrum of AuNPs@SiNWs aqueous solution with a concentration of 70 μg/mL. Inset shows a corresponding photo of the AuNPs@SiNWs sample. (b) Absorbance at 808 nm vs AuNPs@SiNWs concentration. Solid line is the linear fit using the analysis tool in Origin software with R2 = 0.9979.

absorption.43,44 Moreover, a relationship between the absorbance at 808 nm and the concentration of AuNPs@SiNWs is given in Figure 2b. Notably, there is a good linear correlation (R2 = 0.9979) between them when the concentration is below 200 μg/mL (Figure 2b), yielding a fitting relation as follow y = 0.001 + 0.008x

(1)

where x is the concentration of AuNPs@SiNWs (μg/mL) and y is the absorbance at 808 nm. For free SiNWs, that is, SiNWs without AuNPs decoration, a linear correlation (R2 = 0.9997) between the absorbance at 808 nm and the concentration was also observed; however, the concentration would be below 100 μg/mL owing to poor aqueous dispersibility of free SiNWs (Supporting Information Figure S3). In our study, the concentrations of AuNPs@SiNWs and free SiNWs were determined from the absorbance at 808 nm. The AuNPs@SiNWs aqueous solution was irradiated with an 808 nm NIR laser at a power density of 2 W/cm2 with water, phosphate buffered saline (PBS), and RPMI 1640 medium as controls. In marked contrast to the control groups yielding no obvious temperature increase, the AuNPs@SiNWs solution showed a rapid rise in temperature upon exposure to the laser in a short time (Figure 3a). Moreover, a significant dosedependent increase was observed with higher concentration

Figure 3. Photothermal effect of AuNPs@SiNWs (a) and free SiNWs (b) solutions showing temperature increase as a function of NIR irradiation (2W/cm2) time and sample concentration. AuNPs@SiNWs solutions that showed rapid rise in temperature was noted for the AuNPs@SiNWs solution, whereas water, PBS, and RPMI 1640 medium showed little change in temperature upon NIR laser irradiation. 1847

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by NIR laser irradiation in the presence of PEG-AuNPs@ SiNWs. We further studied the cytotoxicity of PEG-AuNPs@SiNWs toward KB cells to assess the photothermal effect. The mixture of cells and PEG-AuNPs@SiNWs (75, 150, 300 μg/mL) was exposed to NIR irradiation (808 nm, 2 W/cm2) for different times (1−3 min), and then cell suspensions were diluted for 50 fold with cell culture medium and transferred to 96-well plates. After 24 h incubation, the cell viability was determined by measuring mitochondrial dehydrogenase activity with MTT assay. The results show that without laser irradiation PEGAuNPs@SiNWs even of high concentrations (100−300 μg/ mL) produced feeble toxicity to the cells in 30-min incubation (Supporting Information Figure S5). Moreover, as the final concentration of PEG-AuNPs@SiNWs after 50-fold dilution was equal to or smaller than 6 μg/mL in the following 24 h incubation for MTT assays, thus they were also very harmless to the cells (Figure 4a). Indeed, as indicated by the black line in Figure 6a, without laser irradiation little decrease in cell viability was detected when cells were exposed to 0−300 μg/mL PEGAuNPs@SiNWs. On the other hand, in the absence of PEGAuNPs@SiNW, all control cells survived the 3 min NIR irradiation, since the temperature rise was only 2 °C (see black columns in Supporting Information Figure S6a). These results demonstrated that PEG-AuNPs@SiNWs or NIR laser irradiation alone had little or no effect on cell viability. On the contrary, when KB cells were exposed to PEG-AuNPs@SiNWs and irradiated with NIR laser, a significant concentration- and time-dependent decrease in cell viability was observed with larger concentrations and longer irradiation time yielding lower cell viability due to significant temperature increase. Typically, the temperature of the cells and PEG-AuNPs@SiNWs (300 μg/mL) mixture rose to 38.9 or 47.6 °C after 2 or 3 min irradiation (Supporting Information Figure S6a), respectively, which is a sufficiently high temperature to kill the cells.25 Microscopic studies further confirmed the biochemical assays of cell viability. As shown in Figure 6b, while no obvious change in cellular morphology was observed in the absence of PEGAuNPs@SiNWs or irradiation, KB cells became increasingly round and nonadherent with increasing PEG-AuNPs@SiNWs concentrations and irradiation time. To avoid the possibility of inadvertent selection of particularly heat-sensitive cells, we also evaluated the photothermal effect of PEG-AuNPs@SiNWs on two other cancer cell lines, i.e., human lung carcinoma cells (A549 cells) and human epithelial cervical cancer cells (Hela cells). Figure 7 displays the corresponding cell viability of PEG-AuNPs@SiNWs-incubated

Figure 4. (a) Cytotoxicity comparison of AuNPs@SiNWs and PEGAuNPs@SiNWs exposed to KB cells for 24 h. Cell viability was calculated as a percentage of the viability of the control (untreated) cells, which was set at 100%. The results are expressed as the means ± SD from three or four independent tests. (b) Photothermal effect of PEG-AuNPs@SiNWs samples. Temperature increase as a function of NIR irradiation (2 W/cm2) time depends on sample concentration. Rapid rise of temperature was noted in PEG-AuNPs@SiNWs aqueous solutions, revealing heat generation due to NIR absorption by PEGAuNPs@SiNWs dispersion.

NIR laser exposure, dead cells would be stained blue by treatment with 0.4% trypan blue for 10 min. The optical microscope images showed no changes for the control groups, that is, cells cultured without PEG-AuNPs@SiNWs with (Figure 5a) or without NIR laser irradiation (Figure 5b). Moreover, little cell destruction was observed without laser irradiation even in the presence of PEG-AuNPs@SiNWs (Figure 5c). In striking contrast, nearly all KB cells cultured with PEG-AuNPs@SiNWs were stained blue (Figure 5d) after 3 min irradiation, showing the cancer cells were fully destructed

Figure 5. Optical images of KB cells. (a) Control cells, (b) control cells after laser irradiation, (c) cells cultured with 150 μg/mL PEG-AuNPs@ SiNWs, and (d) cells cultured with 150 μg/mL PEG-AuNPs@SiNWs after 3 min 2 W/cm2 808 nm laser irradiation. Blue color indicates dead cells (Trypan blue test). Scale bar = 20 μm. 1848

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threshold NIR laser densities (2 W/cm2) and irradiation durations (2−3 min) of PEG-AuNPs@SiNWs for effective cell destruction are smaller than or comparable to those of the wellstudied nanomaterials (e.g., gold nanorods, gold nanoshell, etc.)-based photothermal agents24−27 (NIR laser densities (∼4−35 W/cm2) and irradiation durations (>4 min)). In conclusion, we report AuNPs@SiNWs nanohybrid as the first example of silicon nanowires-based NIR hyperthermia agent for highly efficient cancer cell destruction. Significantly, the AuNPs@SiNWs nanohybrid exhibits distinctive photothermal effects under NIR laser irradiation, yielding temperature rise up to 60 °C under 3 min exposure to a low-power laser (808 nm, 2 W/cm2). In vitro experiment demonstrates that AuNPs@SiNWs are highly efficacious and universal for destruction of three different cancer cells. Given that SiNWs can be readily prepared with high reproducibility and low cost, AuNPs@SiNWs may serve as a practical and powerful NIR hyperthermia agent for photothermal cancer therapy, rivaling or complementing the state-of-the-art hyperthermia cancer agents. Although better understanding of AuNPs@SiNWs in vitro and in vivo behavior, as well as effect of length or diameter of SiNWs on photothermal conversion, demands further investigation, the present findings suggest new opportunities for novel silicon nanomaterials-based bioapplications, particularly in disease treatment.

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Figure 6. Photothermal destruction of KB cancer cells. (a) Viability of KB cells versus NIR laser (808 nm, 2W/cm2) and time (0, 1, 2, 3 min) as a function of PEG-AuNPs@SiNWs concentrations. (b) Morphology of KB cells incubated with PEG-AuNPs@SiNWs of different concentrations and exposed to different laser irradiation time. Scale bar = 20 μm.

ASSOCIATED CONTENT

S Supporting Information *

Experimental methods, Figure S1−S8, and corresponding discussion. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] (S.T.L.); [email protected] (Y.H.). Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by National Basic Research Program of China (973 Program 2012CB932400, 2012CB932600), NSFC (30900338, 51132006, 51072126), the Research Grants Council of HKSAR (CityU5/CRF/08, N_CityU108/08, and CityU 101608), and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Figure 7. Cell viability of (a) A549 cells and (b) Hela cells. The cells were exposed to NIR laser (808 nm, 2W/cm2) for different time (0, 1, 2, 3 min) as a function of PEG-AuNPs@SiNWs concentration.

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A549 and Hela cells after 3-min laser irradiation. Similar to that of KB cells, the cell viability of both A549 and Hela cells was gradually reduced with increasing SiNWs concentration and irradiation time. Particularly, cells incubated with 150 μg/mL PEG-AuNPs@SiNWs were nearly all dead upon 2-min irradiation. The corresponding temperature increase was also monitored and shown to follow a similar tendency to that of KB cells (Supporting Information Figure S6b and S6c), demonstrating that such SiNWs-based hyperthermia effects are quite universal to a range of cell lines for cancer cell destruction. Microscopic studies further confirmed the biochemical assays of cell viability, in which both kinds of cells became round after treatment of the PEG-AuNPs@SiNWs (Supporting Information Figure S7 and S8). Note that the

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