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Gold Nanorods

Gold Nanorods

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Properties of Gold Nanorods

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Gold nanorods have several properties that make them extremely useful for cancer treatment. One of these is that gold nanorods are biocompatible, meaning that they are non-toxic and can survive inside of an organism. [1] Also, the ideal particle size for gold nanorods used for cancer treatment is around 40 nm in length and 10 nm in diameter, which allows the rods to be small enough to circulate through the body and also to be excreted naturally. [2] Gold nanorods optical properties are a large reason that they are used in cancer treatment. Gold nanorods emit surface wavelengths that fall into the infrared part of the light spectrum. This is a result of the resonance of incident and surface plasma. Also, the absorption cross sections of gold nanorods are 10^5 times larger than commonly used dye like material, this allows for PPTT therapy to take place, and Scattering Cross Section is 10^3 times larger than fluorescent dyes. This, essentially, allows more light to be absorbed and scattered and makes the gold nanorods easier to identify. In fact, this allows for individual molecules to be identified using single-molecule Raman detection. [3] The final properties that gold nanorods have that are associated with cancer research and treatment are its plasmonic properties. The higher the absortion/scattering ratio is, the more applicable plasmonic photothermal therapy is, as more light is absorbed therefore creating more thermal energy, which can be used to destroy cancer cells. As the particle size of gold nanorods decreases, the absorbance:scattering ratio increases, allowing for greater photothermal heat conversion and therefore potentially enhancing PPTT efficiency with decreased particle size. Secondly, another plasmonic property associated with photothermal heat conversion is the electric field at the surface of the AuNR. Gold nanorods emit a strong electromagnetic field and as absorption increases, the strength of the electromagnetic field also increases. Since the field strength is derived from absorbance, not scattering, greater absorbance with smaller AuNRs would indicate a stronger field, which in turn would result in greater photothermal heat conversion and, again, enhanced PPTT efficacy. These plasmonic properties, along with its optical properties and biocompatibility properties, make gold nanorods ideal for cancer treatment. [4]

Gold Nanorod Synthesis

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There are several methods that can be used to create gold nanorods. However, the most popular of these methods is the seed-mediated growth method. Nanorods are first synthesized by chemical reduction of gold salt with a strong reducing agent (sodium borohydride) in the presence of a capping agent (citrate) In order to prepare the gold nanoparticles, a growth solution containing HAuCl4 and C16TAB is mixed with freshly prepared ascorbic acid solution and then added to a seed solution to generate gold nanorods. Different size nanorods can be synthesized using different solutions. Although gold nanospheres are also formed in this synthesis, they can be readily removed via centrifugation, which is a process that separates liquids. The CTAB is toxic to bio-molecules and cells and after centrifugation a small surfactant layer of CTAB remains on the gold nanorods. One way to remove this toxic surfactant layer while preventing simultaneous aggregation of the nanoparticles is by increasing the temperature of the solution and sonicating the nano rods. 11-Mercaptoundecanoic acid (MUDA) can be used used as a thiol to react with the gold nano rods and replace the CTAB as a nontoxic surfactant. Once this is done, the nano rod surface is fully activated and ready for biofunctionalization. [5]

Aptamer Panels

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One useful application of gold nanorods is that they provide good surfaces on which DNA or RNA aptamers can be attached. Aptamers are molecules with unique 3-dimensional structures that allow them to bind to specific target molecules or specific receptors on target cells, such as cancerous tumor cells. The small size, lack of immunogenicity, and ease of synthesis of aptamers make them very suitable for molecular recognition as opposed to other molecular probes such as antibodies.To allow the cancerous cells to be visibly detected, the aptamers are fluorescently labeled. Single aptamers aren’t easily detected, so instead panels with higher amounts of aptamers are used. Au-Ag nanorods can work well as these panels, providing a surface on which up to 80 fluorescently labeled aptamers per 12 nm X 56 nm of Au-Ag nanorod can be attached.[6] One example of these aptamers being applied is the use of cytochrome c-specific binding aptamers to make mesoporous silica-encapsulated gold nano rods efficiently accumulate in the mitochondria of cancer cells. This combination of aptamers and gold nano rods can load various hydrophobic therapeutic agents acting on mitochondria to enhance the therapeutic efficiency of chemotherapy and simultaneously depress the toxic side effects. In addition, near-IR treatment can induce cytochrome c release and initiation of the mitochondrial pathway of apoptosis. This organelle-targeted drug delivery allows for high efficiency of positive therapeutic effects. Cite error: A <ref> tag is missing the closing </ref> (see the help page).

Cancer Treatment

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Using near infrared (NIR) lasers to photothermally increase the temperature of the Au nanorods can result in quick death of targeted cancer cells. The use of gold nanorods for this purpose is called plasmonic photothermal therapy (PPTT). The nanorods specifically bind themselves to the malignant cancer cells due to the over-expression of epidermal growth factor receptor compared to normal cells. This makes it easier to identify the malignant cells versus the non-malignant cells. The nanorods scatter red light in a dark field, which can be observed using a laboratory microscope and clearly makes the cancer cells stand out because of the high ratio of nanorods that have accumulated on their surface. Once they are identified, they are targeted by the near infrared laser to be photothermally destroyed. The reason this works so well is because malignant cells require about half of the laser energy to be photothermally destroyed of healthy cells. This way, healthy cells remain unharmed in the process and the tumerous cells are eradicated. Using gold nanorods to kill cancer is an excellent non-invasive technique without the toxic effects induced by chemo-therapy and the invasive techniques used in surgery. Nanorods continue to be a highly researched topic within the bio-medicinal field. Continued research involves finding the ideal molecular size concentration because different concentrations and sizes display different properties. Also, NIR lasers cannot reach internal organs affected by more serious cancers, and most current research is still focused on epithelial cancers. However, nanorods continue to be smaller and more effective, and these various methods continue to improve. [7]

References

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  1. ^ Progress in Cancer Diagnosis and Treatment Based on Gold Nanorods Tianmu Zhang Changli Li Lihui Zhao1 Yu Ren1 Guo Moran Xihe Zhang1 Hongxing Cai 29 August - 1 September 2012, Xi’an, China
  2. ^ (Raman reporter-coated gold nanorods and their applications in multimodal optical imaging of cancer cells Li Jiang & Jun Qian & Fuhong Cai & Sailing He).Received: 15 November 2010 /Revised: 10 February 2011 /Accepted: 9 March 2011 / Published online: 1 April 2011
    1. Springer-Verlag 2011
  3. ^ Progress in Cancer Diagnosis and Treatment Based on Gold Nanorods Tianmu Zhang Changli Li Lihui Zhao1 Yu Ren1 Guo Moran Xihe Zhang1 Hongxing Cai 29 August - 1 September 2012, Xi’an, China
  4. ^ The Most Effective Gold Nanorod Size for Plasmonic Photothermal Therapy: Theory and In Vitro Experiments Megan A. Mackey, Moustafa R. K. Ali,† Lauren A. Austin,† Rachel D. Near,† and Mostafa A. El-Sayed* Laser Dynamics Laboratory, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332-0400, United States
  5. ^ Progress in Cancer Diagnosis and Treatment Based on Gold Nanorods Tianmu Zhang Changli Li Lihui Zhao1 Yu Ren1 Guo Moran Xihe Zhang1 Hongxing Cai 29 August - 1 September 2012, Xi’an, China ).
  6. ^ Cancer Cell Targeting Using Multiple Aptamers Conjugated on Nanorods Yu-Fen Huang ,† Huan-Tsung Chang ,‡ and Weihong Tan *† Center for Research at Bio/nano Interface, Department of Chemistry and Shands Cancer Center, University of Florida, Gainesville, Florida 32611, and Department of Chemistry, National Taiwan University, Taipei, Taiwan Anal. Chem., 2008, 80 (3), pp 567–572 DOI: 10.1021/ac702322j Publication Date (Web): January 1, 2008 Copyright © 2008 American Chemical Society
  7. ^ Progress in Cancer Diagnosis and Treatment Based on Gold Nanorods Tianmu Zhang Changli Li Lihui Zhao1 Yu Ren1 Guo Moran Xihe Zhang1 Hongxing Cai 29 August - 1 September 2012, Xi’an, China