Tumor-specific Nano-entities for Optical Detection and Hyperthermic Treatment of Breast Cancer

  • Hanzhu Jin
  • Bin Hong
  • Sham S. Kakar
  • Kyung A. Kang
Part of the Advances In Experimental Medicine And Biology book series (AEMB, volume 614)


The ultimate goal of this study is to develop a tumor-specific multi-functional, nano-entity that can be used for both cancer detection and treatment. Low heat (42~45°C) hyperthermia is an effective cancer treatment method with little side effect. Magnetic nanoparticles, such as Fe3O4, can be heated by alternating electromagnetic (AEM) fields at well selected frequencies, without heating normal tissue. Nanogold particles (NGPs) are effective optical absorbers and also excellent fluorescent enhancers. Therefore, coating gold on Fe3O4 particles can enhance the optical contrast as well as keeping the particle property for hyperthermia. Indocyanine green (ICG), a FDA approved fluorophore, has a very low quantum yield, and its fluorescence can be enhanced by linking ICGto gold-coated Fe3O4 nanoparticles. Luteinizing hormone releasing hormone (LHRH), which has high affinity to breast cancer, can be used for tumor-specific targeting. Our study results showed: Fe3O4 particles at a size range of 10~30 nm can be heated well by an AEM field at a rate of 18°C/wt%-minute; the fluorescence of ICG was extensively enhanced by NGPs; LHRH-coated gold nanoparticles provided as much cancer specificity as LHRHalone. Combining these properties in one entity, i.e.,LHRH/ICGlinked, gold-coated Fe3O4 nanoparticles, can be a tumor-specific nano-agent for optical detection and electro-magnetically induced hyperthermia for breast cancer.


Indocyanine Green Gold Layer Optical Detection Luteinizing Hormone Release Hormone Diffuse Optical Tomography 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    F. Kristian Storm, Hyperthermia in Cancer Therapy, (G. K. Hall Medical Publishers, Boston, MA, 1983).Google Scholar
  2. 2.
    S. Sharma, S.P. Sandhu, F. D. Patel, S. Ghoshal, B. D. Gupta, and N. S. Yadav, Cervix cancer and hyperthermia: Side-effects of local hyperthermia: results of a prospectively randomized clinical study, Int. J. Hyperthermia, 6 (2), 279–285, (1990).PubMedCrossRefGoogle Scholar
  3. 3.
    T. Ohtsubo, H. Igawa, T. Saito, H. matsumoto, H. Park, C. W. Song, E. Kano, and H. Saito, Enhancement of cell killing by induction of apoptosis after treatment with mild hyperthermia at 42°C and cisplatin, Radiation Research, 156, 103–109, (2001).PubMedCrossRefGoogle Scholar
  4. 4.
    A. Jordan, R. Scholz, P. Wust, H. Fahling, and R. Felix, Magnetic fluid hyperthermia (MFH): cancer treatment with AC magnetic field induced excitation of biocompatible superparamagnetic nanoparticles J. Magn. Magn. Mater. 201, 413–419, (1999).CrossRefGoogle Scholar
  5. 5.
    P. Tartaj, M.P. Morales, S. Veintemillas-Verdaguer, T. Gonz'alez-Carreno, and C.J. Serna, The preparation of magnetic nanoparticles for applications in biomedicine, J. Phys. D: Appl. Phys. 36, R182–197, (2003).CrossRefGoogle Scholar
  6. 6.
    D. Bahadur, and J. Giri, Biomaterials and magnetism, Sadhana, 28 (3 and 4), 639–656, (2003).CrossRefGoogle Scholar
  7. 7.
    S. Mornet, S. Vasseur, F. Grasset, and E. Duguet, Magnetic nanoparticle design for medical diagnosis and therapy, J. Mater. Chem., 14, 2161–2175, (2004).CrossRefGoogle Scholar
  8. 8.
    S. J. Oldenburg, J. B. Jackson, S. L. Westcott, and N. J. Halas, Infrared extinction properties of gold nanoshells, Applied Physics Letters, 78 (19), 2897–2899, (1999).CrossRefGoogle Scholar
  9. 9.
    C. H. Chou, C. D. Chen, and C. R. Wang, Highly Efficient, Wavelength-Tunable, Gold Nanoparticle Based photothermal Nanoconvertors, J. Phys. Chem. B, 109, 11135–11138, (2005).PubMedCrossRefGoogle Scholar
  10. 10.
    S. Achilefu, R. B. Dorshow, J. E. Bugaj, and R. Rajagopalan, Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging. Invest Radiol, 35:479–485, (2000).PubMedCrossRefGoogle Scholar
  11. 11.
    C. D. Geddes, A. Parfenov, D. Roll, M. J. Uddin, and J. R. Lakowicz, Fluorescence spectral properties of indocyanine green on a roughened platinum electrode: Metal-enhanced fluorescence, Journal of Fluorescence, 13 (6), 453–457, (2003).CrossRefGoogle Scholar
  12. 12.
    B. Hong and K.A. Kang, Biocompatible, nanogold-particle fluorescence enhancer for fluorophore mediated, optical immunosensor, Biosensors and Bioelectronics, 21(7), 1333–1338, (2006).PubMedCrossRefGoogle Scholar
  13. 13.
    R. Eckert, D. Randall, and G. Augustin, Animal Physiology, 3rd Edition, W. H. Freeman and Company, New York, 435–473, (1988).Google Scholar
  14. 14.
    S. S. Kakar, L. C. Musgrove, D. C. Devor, J. C. Sellers, and J. D. Neill, Cloning, sequencing, and expression of human gonadotropin releasing hormone (GnRH) receptor. Biochem. Biophys. Res. Commun. 189, 289–295, (1992).PubMedCrossRefGoogle Scholar
  15. 15.
    M. Preuss, W.G. Schmidt, and F. Bechstedt, Coulombic amino group-metal bonding: Adsorption of adenine on Cu (110), Physical Review Letters, 94, 236102–4, (2005).PubMedCrossRefGoogle Scholar
  16. 16.
    S. S. Kakar, W. E. Grizzle, and J. D. Neill, The nucleotide sequences of human GnRH receptors in breast and ovarian tumors are identical with that found in pituitary, Mol. Cell. Endocrinol. 106, 145–149, (1994).PubMedCrossRefGoogle Scholar
  17. 17.
    S. S. Kakar, M. T. Malik, S. J. Winters, and W. Mazhawidza, Gonadotropin-releasing hormone receptors: structure, expression, and signaling transduction. Vitam Horm. 69, 151–207, (2004).PubMedGoogle Scholar
  18. 18.
    H. Jin and K. A. Kang, Fluorescent mediated detection of Heterogeneity in a highly scattering media, Adv. Exper. Med. Bio., 566, 167–172, (2005).CrossRefGoogle Scholar
  19. 19.
    T. L. Troy, B. W. Pogue, E. D. Genety, S. B. Poplack, O. L. Osterburg, and K. D. Paulsen, Spectroscopic diffuse optical tomography for the quantitative assessments of hemoglobin concentration and oxygen saturation in human breast tissue, Appl. Opt., 38(25), 5480–5490, (1999).Google Scholar
  20. 20.
    A.L. Honar and K.A. Kang, Effect of the source and detector configuration on the detectability of breast cancer, Comp. Biochem.Physio - Part A: Molecular & Integrative Physiology, 132(1), 9–15, (2002).CrossRefGoogle Scholar
  21. 21.
    D. F. Bruley, Pulse reduction code written for process identification (personal communication), (1974).Google Scholar
  22. 22.
    S. S. Kakar, S. J., Winters, W. Zacharias, D. M. Miller, and S. Flynn, Identification of distinct gene expression profiles associated with treatment of LbetaT2 cells with gonadotropin-releasing hormone agonist using microarray analysis. Gene. 308, 67–77, (2003).PubMedCrossRefGoogle Scholar
  23. 23.
    H. Jin and K. A. Kang, Application of Novel Metal Nanoparticles as Optical/Thermal Agents in Optical Mammography and Hyperthermic Treatment for Breast Cancer, Proceedings of the 33rd ISOTT Annual Meeting, August 28-September 2, Brisbane, Australia, Manuscript Submitted, (2005).Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Hanzhu Jin
    • 1
  • Bin Hong
    • 1
  • Sham S. Kakar
    • 2
  • Kyung A. Kang
    • 1
  1. 1.Department of Chemical Engineering, Department of MedicineUniversity of LouisvilleLouisvilleUSA
  2. 2.Department of MedicineUniversity of LouisvilleLouisville

Personalised recommendations