July 30 2017 by Juili Kelvekar

At the nanoscale some materials exhibit extraordinary properties. Arguably, the most widely utilized inorganic nanomaterial is gold. When gold nanoparticles (AuNPs) are irradiated with certain wavelengths of light they form dipole oscillation that results in Surface Plasmon Resonance (SPR). Essentially, light causes a vibration in the electron cloud, resonating at a particular set of frequencies. Due to this property, AuNPs have increasingly found utility in novel medical applications and research.


Here 4 emerging medical uses of plasmonic gold nanoparticles are examined.

1. Photoacoutic Imaging: Gold nanoparticles, specifically gold nanorods, are used as contrast agents in photoacoustic imaging due to strong and tunable absorption in the near infrared region (NIR). At NIR wavelengths light penetrates more deeply through tissues enabling enhanced imaging of structures. Further, gold nanoparticles optical absorption is orders of magnitude higher than conventional dyes.1 When AuNPs are illuminated with a pulsed laser source, they efficiently convert the transient light energy to transient heat energy. This results in thermal expansion of the surrounding medium, and creates an ultrasonic sound wave which is detected by ultrasound transducers to produce a high resolution image. If the gold nanoparticles are bound to an antibody which highlights a particular pathology, then gold nanoparticles can specifically label diseased tissues; making for a powerful diagnostic tool.

    Examples of AuNPs as exogenous contrast for photoacoustic imaging:

          • Assistance with prostate cancer detection,2
          • Detection of circulating metastatic melanoma cells,3
          • Sentinel lymph node diagnosis 4,5
          • Characterization of atherosclerotic plaque,6
          • Functional brain imaging,7
          • Imaging of developing vasculature during early tumor growth.8
     
    2. Photodynamic Therapy: Photosensitizer decorated AuNPs can be used effectively in photodynamic therapy. Irradiation at a light wavelength that corresponds to the SPR peak prompts the attached photosensitizer to produce Reactive Oxygen Species (ROS). The energy transfer during the formation of ROS can cause irreversible damage to targeted cells or tissues.9

    Examples of Photodynamic Therapy using AuNPs:

          • Treatment of precancerous cells in oncology 10,11, sun-damaged skin, and acne.12,13
          • Treatment of inflammatory disorders and cutaneous infections.14

     

    3. Photothermal Therapy:  The released thermal energy from light irradiation of AuNPs is shown to help kill targeted cells. Gold nanoparticles are targeted to a tissue of interest and then are illuminated with a light source, generally a monochromatic light source with a peak wavelength corresponding to the SPR of the gold nanoparticle. The gold nanoparticles absorbs light and releases heat. Since AuNPs are better light absorbers than tissue, when localized to a specific tissue, such as a cancerous tumor, gold nanoparticles can successfully kill the diseased cells via hyperthermia while sparing the surrounding healthy tissues.

    Examples of Photothermal Therapy using AuNPs:

          • Targeted detection and treatment of carcinoma,15
          • Cancer cell imaging.16

     

    4. Radiation Therapy: In radiation therapy, high energy ionizing radiation is used to shrink tumors and kill cancer cells. Disadvantages of single agent radiation therapy include injuring surrounding healthy tissue, only low intensities reach tumors that are deep inside the body, and cells can develop resistance to radiation. These disadvantages can be overcome by using gold nanoparticles as a radiation sensitizer. AuNPs are biocompatible and can be delivered efficiently to the diseased site to enhance the effect of radiation. Additionally, the size and shape of the AuNPs can be tuned for therapeutic delivery requirements and to achieve optimum effect.17, 18 Overall, by introducing gold nanoparticles, the radiation dose can be significantly reduced while maintaining cancer-localized therapeutic benefit.

    THE GOLDEN VALUE OF AuNPs

    AuNPs are favored for theranostics (therapy + diagnostics) over other plasmonic nanoparticles because they maintain biological compatibility, can be synthesized easily, can be produced in different shapes and sizes depending upon application, and can be targeted to a wide variety of pathologies in the human body.

     

    Explore More:

    Plasmonc Properties of NanoparticlesPhotoacoustic Imaging

    References:

    1. Wanwan Li, Xiaoyuan Chen “Gold nanoparticles for photoacoustic imaging” Nanomedicine (Lond). 2015 Jan; 10(2): 299-320 DOI: 10.2217/nnm.14.169
    2. Agarwal A., S. Huang, M. O’Donnell, K. C. Day, N. Kotov, S. Ashkenazi “Targeted gold nanorod contrast agent for prostate cancer detection by photoacoustic imaging” J. Appl. Phys.  DOI:  http://dx.doi.org/10.1063/1.2777127
    3. Galanzha El, Shashkov EV, Spring PM, Suen JY, Zharov VP “In vivo, noninvasive, label-free detection and eradication of circulating metastatic melanoma cells using two-color photoacoustic flow cytometry with a diode laser” Cancer Res. 2009 Oct 15;69(20): 7926-34. DOI: 10.1158/0008-5472.CAN-08-4900.Epub 2009 OCT 13
    4. Luke, Geoffrey P., et al. "Silica-coated gold nanoplates as stable photoacoustic contrast agents for sentinel lymph node imaging." Nanotechnology 24.45 (2013): 455101. DOI: 10.1088/0957-4484/24/45/455101
    5. Luke, Geoffrey P., et al. "Sentinel lymph node biopsy revisited: ultrasound-guided photoacoustic detection of micrometastases using molecularly targeted plasmonic nanosensors." Cancer research 74.19 (2014): 5397-5408. DOI: 10.1158/0008-5472
    6. Iulia Graf, Jimmy Su, Doug Yeager, James Amirian, Richard Smalling Stanislav Emelianov “Methodical study on plaque characterization using integrated vascular ultrasound, strain and spectroscopic photoacoustic imaging” SPIE 7899, Photons Plus Ultasound: imaging and sensing 2011, 789902 (February 10, 2011), DOI:10.1117/12.875689
    7. Hu S, Maslov K, Tsytsarev V, Wang LV “Functional transcranial brain imaging by optical-resolution photoacoustic microscopy” J. Biomed Opt. 2009 Jul-Aug; 14(4):040503. DOI: 10.1117/1.3194136
    8. Yeqi Lao, Da Xing, Sihua Yang and Liangzhong Xiang “Noninvasive photoacoustic imaging of the developing vasculature during early tumor growth” 2008 Phys. Med. Biol. 53 4203 DOI: https://doi.org/10.1088/0031-9155/53/15/013
    9. Eun, Ji Hong, Dae Gun Choi, Min Suk Shim “Targated and effective photodynamic therapy for cancer using functionalized nanomaterials” Acta Pharm Sin B. 2016 Jul;6(4):297-307 DOI: 10.1016/j.apsb.2016.01.007. Eupub 2016 Apr 16
    10. Dolmans DE, Fukumura D, Jain RK “Photodynamic therapy for cancer” Nat Rev Cancer 2003 May, 3(5):380-7, PMID: 12724736, DOI: 10.1038/nrc1071
    11. Mroz P, Yaroslavsky A, Kharkwal GB, Hamblin MR “Cell death pathways in photodynamic therapy of cancer” Cancers (Basel).  2011; 3(2):2516-39. DOI: 10.3390/cancers3022516
    12. Darlenski R, Fluhr JW “Photodynamic therapy in dermatology: past, present and future” J Biomedical Opt. 2013 Jun; 18(6):061208. DOI: 0.1117/1.JBO.18.6.061208
    13. Kim Bj, Lee HG, Woo SM, Youn JI, Suh DH “Pilot study on photodynamic therapy for acne using indocyanine green and diode laser” J Dermatol. 2009 Jan; 36(1): 17-21. DOI: 10.1111/j.1346-8138.2008.00580.x.
    14. Aurelie Reinhard, William Sandborn, Hassan Melhem, Lina Bolotine, Mathias Chamaillard, Laurent Peyrin-Biroulet “Photodynamic therapy as a new treatment modality for inflammatory and infectious conditions” Expert review of clinical immunology, volume 11, 2015 – Issue 5. http://dx.doi.org/10.1586/1744666X.2015.1032256
    15. Ivan H, Xiaohua Huang, Moatafa El-Sayed “Selective laser photo-thermal therapy of epithelial carcinoma using anti-EGFR antibody conjugated gold nanoparticles” Cancer letters, volume 239, Issue 1, 28 July 2006, pages  129 – 135. https://doi.org/10.1016/j.canlet.2005.07.035
    16. Xiaohua Huang, Ivan H, El-Sayed, Wei Qian “Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods” J. Am. Chem. Soc., 2006, 128(6), pp2115-2120, DOI: 10.1021/ja057254a
    17. Jeremic B, Aguerri AR, Filipovic N “Radiosensitization by gold nanoparticles” 2013 Aug; 15(8):593-601. DOI: 10.1007/s12094-013-1003-7. Epub2013 Jan 29
    18. Atkinson R, Zhang M, Diagaradjane P, Peddibhotla S, Contreras A, Hilsenbeck, Woodward W, Krishnan s, Chang J, Rosen J  “Thermal enhancement with optically activated gold nanoshells sensitizes breast cancer stem cells to radiation therapy” Vol 2, Issue 55, pp. 55ra79 DOI: 10.1126/scitranslmed.3001447