Title:
Development of Novel Therapeutic Techniques using Photothermal Effect of Gold Nanorods
Takuro Niidome （新留琢郎）
Graduate School of Science and Technology, Kumamoto University
熊本大学大学院自然科学研究科 産業創造工学専攻 物質生命化学講座
Abstract:
The development of systems for the delivery of nanoparticles to tumor tissues enables us to image and treat tumors by taking advantage of the unique optical characteristics of the nanoparticles. Among these, gold nanoparticles have potential as a heating device for photothermal therapy, and as contrast agents for optical and photoacoustic imaging [1,2]. Gold nanorods in particular have attracted much attention in the fields of therapeutics and diagnostics?so-called theranostics?because gold nanorods show a strong absorption band in the near-infrared light region; this is the region in which the maximum penetration of light into tissues occurs, corresponding to longitudinal surface plasmon resonance of free electrons [3]. The absorbed light energy is converted to heat, so-called photothermal effect.
Recently, we succeeded in preparing biocompatible gold nanorods by modifying PEG chain [4,5]. The PEG-modified gold nanorods showed long lasting circulation after intravenous injection. Furthermore, modification of gold nanorods with thermosensitive polymer ( N -isopropylacrylamide) gel allows the nanorods to accumulate to specific site, to which near infrared light was irradiated. Phase transition of the gel layer to hydrophobic triggered by photothermal effect of the gold nanorods would contribute to bind the gold the irradiated site [6].
To achieve a controlled release system that can be triggered by irradiation of near infrared light, gold nanorods were modified with double-stranded DNA. When the modified gold nanorods were irradiated by near-infrared light, the single-stranded DNA (ssDNA) was released from the gold nanorods due to the photothermal effect. The amount of released ssDNA was dependent upon the power and exposure time of light irradiation. Release of ssDNA was also observed in tumors grown on mice after light irradiation. It will be a basis of controlled release system of functional oligonucleotides, e.g., siRNA, antisense oligonucleotide, decoy oligonucleotide, and aptamers, responding to near infrared light irradiation.
Next, we constructed a transdermal protein delivery system. We prepared solid-in-oil (S/O) dispersion containing gold nanorods and ovalbumin [7]. Since the gold nanorods have photothermal effect, the produced heat is expected to increase permeability of skin transiently. The greater enhancement effect on ovalbumin delivery was observed after treatment mouse skins with the S/O dispersion of gold nanorods and irradiation by near infrared light followed by further incubation for 12 h. Production of anti-ovalbumin antibodies in serum of mice treated with the S/O dispersion followed by light irradiation of gold nanorods was observed. This approach will offer a new opportunity for transdermal delivery and skin vaccination system of high molecular proteins/drugs.
References:
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2. D. Pissuwan, T. Niidome, and M. B. Cortie, J. Controlled Release , 2011, 149 , 65.
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4. T. Niidome, M. Yamagata, Y. Okamoto, Y. Akiyama, H. Takahashi, T. Kawano, Y. Katayama, Y. Niidome, J. Control. Release , 2006, 114 , 343.
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6. A. Shiotani, Y. Niidome, T. Mori, Y. Katayama, T. Niidome, Bioconjugate Chem. , 2010, 21 , 2049.
7. D. Pissuwan, K. Nose, R. Kurihara, K. Kaneko, Y. Tahara, N. Kamiya, M. Goto, Y. Katayama, T. Niidome, Small 2011, 7 , 215.
