Many metal nanoparticles (NPs) are being studied for use in photothermal cancer therapy, a non-invasive technique where specific wavelengths of light can be used to excite the NPs, causing local heating that selectively kills cancer cells. These NPs can convert light to heat because of surface plasmon resonance, where electrons oscillate at the surface of the NPs resulting in specific absorbance or scattering. Plasmonic metal NPs have attracted enormous interest because their physical and chemical properties can be tuned by changing the size, shape, and composition of the nanostructures.
Experimental and theoretical results have shown that non-spherical NPs, such as branched or urchin-like ones, exhibit stronger electromagnetic behavior than spherical NPs, making them more effective for photothermal therapy.1 Moreover, anisotropic gold NPs exhibit numerous plasmon resonances in the visible and near-IR range, which depend strongly on polarization. However, anisotropic NPs require long synthesis times, and they are unstable at room temperature. These issues limit their use.
Branched gold NPs can be obtained by several methods, the most common is the seeded growth approach. While the morphology of the resulting NPs can be tuned by several factors in the seeded growth approach,2 the process is lengthy and complicated. Seedless synthesis is another route to save time, but the NP morphology cannot be well-tuned, which limits its efficiency in bio-applications.3 We created a new technique to grow tunable, non-spherical gold/silver NPs using a simple, rapid one-reactor (one pot) process. The spiky, urchin-like NPs that we produce have excellent properties for transforming light into heat, making them effective for destroying cancer cells.
Transmission-electron-microscopy bright-field images of gold/silver nanocrystals synthesized with various gold/silver ratios: (a) 3, (b) 10, (c) 15, (d) 30, (e) 50 and (f) 100.5
Synthesis of various nanoparticle morphologies with different amounts of silver ions.5
By changing the ratio of gold/silver precursors, we can tune the structure of our NPs (see Figure 1). According to Liu et al., halide and silver ions are important to the formation and growth of gold nanostructures.4 The gold/silver ratio governed the morphology of our NPs due to catalytic effect of the silver atoms (see Figure 2). Gold grew from these active sites on the surface of the gold NPs, generating urchin-like gold/silver bimetallic NPs. We found that a lower gold/silver ratio leads to higher amounts of shorter gold tips. For higher gold/silver ratios, NPs with fewer, longer tips (or irregular, quasi-spherical-shaped NPs) were formed. We were able to create spiky urchin-like gold/silver bimetallic NPs from solutions with high concentrations of silver ions.
After we chitosan capped the NPs, they were used for in vitro photothermal ablation of oral cancer SAS cells with a laser wavelength of 800nm, a relatively low power density (1.8 W/cm2), and low concentration of NPs (0.01nM). We found that the SAS cells without NPs were not damaged after exposure under laser irradiation for 5min: see Figure 3(a). In contrast, cells with added NPs experienced significant cell death after laser exposure for 1min: see Figure 3(b) and (c).
Our results are corroborated by simulations (see Figure 4), which reveal that the greatest enhancement of electrical field energy density and dissipative electric energy occurs near the tips of the needle-like structure, which leads to greater heat generation from the tips. These results suggest that our bimetallic urchin-like NPs have great photothermal ablation ability. We expect that when combined with our simple synthesis process, our tunable NPs will be beneficial in bio-applications.
Microscopic images of cells after irradiation by a 800nm laser, stained by trypan blue. (a) SAS cancer cells without NPs, (b-c) oral cancer cells incubated with gold/silver (10:1 ratio) NPs (red dotted squares indicate the irradiation area).5
Field distributions of the urchin-shape gold NPs under X-polarized illumination at 800nm wavelength. (a) Simulation results of the natural logarithm of electrical energy density (color-coded). (b) The distribution of time-averaged resistive heating of the urchin-shape gold NPs.5
Our gold/silver bimetallic urchin-like NPs can be created using a simple one pot process that is faster than previous methods. The structure of our NPs can be tuned by altering the ratio of gold/silver precursors. The highly efficient photothermal ablation, large resistive heat generation, and tunable near-IR absorption characteristics of these urchin-like NPs make them potential nanomaterials for further in vitro and in vivo cancer therapy, Raman scattering enhancement, and catalytic reactions. In the future, we would like to study the combination of these NPs with up-conversion NPs for use in photothermal therapy, using the up-conversion NPs to absorb IR light and emit visible light as an identification marker.
The authors would like to thank the National Science Council of Taiwan, (Contracts Nos. NSC 101-3113-M-002-014-MY3 and NSC 101-3113-P-002-021) for financially supporting this research. They would also like to thank Ms. Chia-Ying Chien of Instrumentation Center, National Taiwan University for TEM experiments, and Ms. Li-Wen Lo of Genomics Research Center, Academia Sinica for confocal microscopy.
Ru-Shi Liu, Liang-Chien Cheng, Jing-Hong Huang, Hao Ming Chen
Department of Chemistry
National Taiwan University
Ru-Shi Liu is currently a professor whose research concerns the field of materials chemistry. He is an author or coauthor of more than 400 publications in international scientific journals. He has also been granted more than 80 patents.
Liang-Chien Cheng is currently a PhD student supervised by Ru-Shi Liu. His current research interests include the synthesis of metallic NPs, nanodiamond, and up-conversion nano materials for bio-applications.
Tsung-Ching Lai, Michael Hsiao, Chung-Hsuan Chen
Genomics Research Center
Kuang-Yu Yang, Din Ping Tsai
Department of Physics
National Taiwan University
Taiwan Hopax Chemicals Manufacturing Company Ltd.
1. F. Hao, C. L. Nehl, J. H. Hafner, P. Nordlander, Plasmon resonances of a gold nanostar, Nano Lett.
7(3), p. 729-732, 2007. doi:10.1021/nl062969c
2. Y. Lee, T. G. Park, Facile fabrication of branched gold nanoparticles by reductive hydroxyphenol derivatives, Langmuir
27(6), p. 2965-2971, 2011. doi:10.1021/la1044078
3. B. K. Jena, C. R. Raj, Seedless, surfactantless room temperature synthesis of single crystalline fluorescent gold nanoflowers with pronounced SERS and electrocatalytic activity, Chem. Mater.
20(11), p. 3546-3548, 2008. doi:10.1021/cm7019608
4. M. Z. Liu, P. Guyot-Sionnest, Mechanism of silver(I)-assisted growth of gold nanorods and bipyramids, J. Phys. Chem. B
109(47), p. 22192-22200, 2005. doi:10.1021/jp054808n
5. L.-C. Cheng, J.-H. Huang, H. M. Chen, T.-C. Lai, K.-Y. Yang, R. S. Liu, M. Hsiao, C.-H. Chen, L.-J. Her, D. P. Tsai, Seedless, silver-induced synthesis of star-shaped gold/silver bimetallic nanoparticles as high efficiency photothermal therapy reagent, J. Mater. Chem.
22(5), p. 2244-2253, 2012. doi:10.1039/C1JM13937A