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A New Era for Cancer Treatment: Goldnanoparticlemediated Thermal Therapies

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A New Era for Cancer Treatment: Goldnanoparticlemediated Thermal Therapies Photothermal Therapy A New Era for Cancer Treatment: Gold-Nanoparticle- Mediated Thermal Therapies Laura C. Kennedy , Lissett R. Bickford , Nastassja A. Lewinski , Andrew J. Coughlin , Ying Hu , Emily S. Day , Jennifer L. West , * and Rebekah A. Drezek * From the Contents 1. Introduction . 2 N anotechnology-based cancer treatment approaches potentially provide localized, targeted therapies that 2. Gold Nanoparticle Design for Photothermal Therapy Applications . 2 aim to enhance effi cacy, reduce side effects, and improve patient quality of life. Gold-nanoparticle-mediated 3. Opportunity #1: Methods to Provide hyperthermia shows particular promise in animal studies, Irradiating Energy to the Tumor. 5 and early clinical testing is currently underway. In this 4. Opportunity #2: Enhancing In-vivo article, the rapidly evolving fi eld of gold nanoparticle Delivery and Biodistribution of Gold thermal therapy is reviewed, highlighting recent literature Nanoparticles . 8 and describing current challenges to clinical translation of the technology. 5. Opportunity #3: Understanding Impact of Gold Nanoparticle Use In vivo . 12 6. Conclusion. 13 small 2010, X, No. XX, 1–15 © 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim wileyonlinelibrary.com 1 reviews L. C. Kennedy et al. 1. Introduction 2. Gold Nanoparticle Design for Photothermal In 2010, the National Institutes of Health estimates that Therapy Applications more than 1.5 million new cases of cancer will have been A diverse range of gold nanoparticles have been explored diagnosed in the United States, with an overall projected cost for use in therapy and imaging applications. Key features to con- [1] of US$263.8 billion. The development of new approaches sider when selecting a particle for hyperthermia are the wave- to improve screening, diagnosis, and treatment of cancer is length of maximal absorption, the absorption cross-section, and an area of intensive research spending and has generated the size of the particle. In this section, the development of several numerous innovations that have enhanced the 5-year survival forms of gold-based nanoparticles used for therapy are discussed, [1] rates of cancer patients. However, these new treatments including gold–silica nanoshells, gold nanorods, gold colloidal [2] also contribute to the rising costs of healthcare. To justify nanospheres, and smaller-diameter NIR-tunable gold nanocages, these increased costs, state-of-the-art treatments should have gold–gold sulfi de nanoparticles, and hollow gold nanoshells. enhanced effi cacy, decreased invasiveness, and fewer side effects than current cancer therapies. While still in a relatively 2.1. Gold–Silica Nanoshells early stage of technological development, gold-nanoparticle- based diagnostic and therapeutic approaches, particularly those based on gold-nanoparticle-mediated hyperthermia, In 2003, Hirsch et al. were the fi rst to demonstrate photo- [ 6 ] Gold–silica have shown promise towards achieving these goals. thermal therapy using gold–silica nanoshells. nanoshells, composed of silica cores with a thin overlay of gold, Gold has been used for the treatment of rheumatoid were the fi rst gold nanoparticles easily tunable to the NIR. By arthritis for many years,[ 3 ] establishing an early precedent for in-vivo use of gold nanoparticles. The wide-ranging varying the size of the silica core and the thickness of the gold utility of gold nanoparticles for medical applications is based shell, the resonance of these nanoshells can span from the visible largely on the unique and highly tunable optical properties to the near infrared. Gold–silica nanoshell fabrication is based that gold nanomaterials provide. When metallic nanoparti- on seed-mediated growth, where ‘seeds’ of gold colloid are cles are exposed to light at their resonance wavelength, the attached to the silica cores, and additional gold is added for com- conduction-band electrons of the nanoparticle generate a pletion of the shell. Similarly to other gold nanoparticles, gold– synchronized oscillation that ultimately terminates in either silica nanoshells have been studied specifi cally for their potential [ 5 , 11 ] two- light scattering or absorption. By carefully designing the size, as imaging contrast agents with darkfi eld microscopy, photon microscopy, [ 17 , 18 ] refl ectance confocal microscopy, [ 19 ] and shape, and composition of gold nanoparticles, the proportion optical coherence tomography (OCT). [ 7 ] In addition to having of light scattering relative to light absorption can be opti- utility in cancer imaging, nanoshells that are strong absorbers mized for the intended application. Gold nanoparticles are can induce cancer cell death by converting light into heat currently being studied for use as imaging contrast agents, [ 4 , 5 ] absorptive heating agents, [ 6 ] and as dual imaging and thera- ( Figure 1 ). Silica-based gold nanoshells have been tested in vitro [ 5 , 20 , 21 ] prostate, [ 22 , 23 ] peutic agents. [ 7 , 8 ] as targeted-therapy probes for human breast, [ 24 ] and liver [ 25 ] cancers. In addition, nanoshells have dem- The most extensively developed of these potential appli- brain, onstrated in-vivo therapeutic effi cacy against xenografted sub- cations, gold-nanoparticle-mediated hyperthermia, is cur- cutaneous tumors in mice and allografted tumors in dogs. [ 26 , 27 ] rently being studied in early clinical trials. [ 9 ] To treat a tumor, gold nanoparticles are systemically administered to the sub- The larger size of gold–silica nanoshells as opposed to many ject and allowed to passively localize to the tumor. [ 10 ] The other gold nanostructures provides an advantage in scatter- tumor is then exposed to an excitation source, such as near- based imaging, but in-vivo delivery may be more challenging infrared (NIR) laser light, [ 6 ] radiowaves, [ 11 ] or an alternating than for smaller particles in some applications. magnetic fi eld. [ 12 ] The gold nanoparticles absorb the incident 2.2. Gold Nanorods energy and convert it into heat, which raises the temperature of the tissue and ablates the cancerous cells by disrupting the cell membrane. [ 13 ] The physical heating mechanism of abla- Gold nanorods, which were developed during the same tive therapies may provide an advantage against chemother- period as gold–silica nanoshells, are generally smaller than apy-resistant cancers, [ 14 ] as well as improved tumor response nanoshells. Like gold–silica nanoparticles, gold nanorods when combined with chemotherapy and radiation. [ 15 , 16 ] The continuing evolution of strategies for gold- L. C. Kennedy , L. R. Bickford , N. A. Lewinski , Y. Hu , Prof. R. A. Drezek nanoparticle hyperthermia has generated a rapidly growing William Marsh Rice University body of literature. In this article, we discuss a number of Dept. of Bioengineering MS-142 recent notable additions to the fi eld including: 1) the use of 6100 Main St., Houston, TX 77005–1892, USA small-diameter, near-infrared, tunable gold nanoparticles, E-mail: [email protected] which will potentially have enhanced in-vivo access to the A. J. Coughlin , E. S. Day , Prof. J. L. West tumor interior; 2) delivery strategies focused on increasing William Marsh Rice University the specifi city and quantity of nanoparticle delivery to Dept. of Bioengineering in-vivo tumors; 3) recent developments in computational 6100 Main St., Houston, TX 77005–1892, USA E-mail: [email protected] modeling of thermal therapy, which could be essential for effective clinical translation. DOI: 10.1002/smll.201000134 2 www.small-journal.com © 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim small 2010, X, No. XX, 1–15 Gold-Nanoparticle-Mediated Thermal Cancer Therapies are easily tuned to the NIR region by simple manipulation of their aspect ratio (length/width) and have been exten- Rebekah Drezek is currently a Professor sively studied for cancer therapy applications. They have in the Departments of Bioengineering and the advantages of small sizes (on the order of 10 nm × Electrical and Computer Engineering at Rice University. She has been on the faculty 50 nm, comparable to gold colloid particles), high absorp- at Rice since 2002 where she conducts basic, tion coeffi cients, and narrow spectral bandwidths. Owing to applied, and translational research at the their distinctive rod shape, gold nanorods have two absorp- intersection of medicine, engineering, and tion peaks corresponding to the longitudinal and transverse nanotechnology towards the development of resonances. The transverse resonance occurs at around minimally invasive, photonics-based imaging 520 nm, while the longitudinal resonance can span the vis- approaches for the detection, diagnosis, and ible and NIR wavelengths. Recent studies have investigated monitoring of cancer. the photothermal heating effi ciencies of NIR-absorbing gold nanoparticles, and both theoretical and experimental results have shown that nanorods offer a superior absorp- tion cross-section versus gold–silica and gold–gold sulfi de Jennifer West is the Department Chair and nanoparticles when normalizing for particle size differences, Cameron Professor of Bioengineering at as well as heating per gram of gold that is at least six times Rice University. Professor West's research faster than gold–silica nanoshells. [ 28–30 ] However, gold–silica focuses on the development of novel biofunc- nanoshells have a signifi cantly larger photothermal trans- tional materials and nanotechnology-based duction cross-section when compared to gold nanorods approaches to cancer treatment. In 2000,
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