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NIR Fluorophore-Hollow Gold Nanosphere Complex for Cancer Enzyme-Triggered Detection and Hyperthermia

  • Jianting Wang
  • Damon Wheeler
  • Jin Z. Zhang
  • Samuel Achilefu
  • Kyung A. Kang
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 765)

Abstract

Hollow gold nanospheres (HGN) may be delicately tuned to absorb near infrared light (NIR) by tailoring the diameter-to-shell ratio. This unique property can be utilized for enhancing the contrast for the NIR and X-ray/CT imaging, and also noninvasive and local, photothermal hyperthermia by conjugating cancer-targeting molecules on the particle surface. In addition, when an NIR fluorophore is placed on the surface of the NIR-tuned HGNs, the fluorescence can be significantly quenched due to the emitted light absorption by the HGNs. Combining the NIR fluorescence quenching property of HGNs and the enzyme secreting nature of cancer, we have developed a novel enzyme-triggered NIR contrast agent for cancer detection with high specificity. NIR fluorophore Cypate (Indocyanine Green based) was conjugated to HGN via a short spacer for fluorescence quenching. The spacer contains an enzyme-substrate-motif (G-G-R) that can be cleaved by urokinase-type plasminogen activator (uPA, a breast cancer enzyme). The nano-complex normally does not emit fluorescence but, in the presence of uPA, the fluorescence was restored, providing high specificity. The enzyme-specific emission allows us to characterize the nature of the cancer (e.g., invasive, metastatic, etc.). Once the cancer is detected, the same HGNs can be used to deliver heat to the cancer site for cancer-specific hyperthermia.

Keywords

NIR fluorophore Hyperthermia 

Notes

Acknowledgments

The authors thank the US Army (DoD) Breast Cancer Program (BC074387) for their financial support. The authors are also grateful to the US National Science Foundation for the financial support for the HGN development.

References

  1. 1.
    Davis ME, Chen Z, Shin DM (2008) Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov 7:771–782CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Shi J, Votruba AR, Farokhzad OC, Langer R (2010) Nanotechnology in drug delivery and tissue engineering: from discovery to applications. Nano Lett 10:3223–3230CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Eustics S, El-Sayed MA (2006) Why gold nanoparticles are more precious than pretty gold: noble metal surface plasmon resonance and its enhancement of the radiative and non-radiative properties of nanocrystals of different shapes. Chem Soc Rev 35:209–217CrossRefGoogle Scholar
  4. 4.
    Hu M, Chen J, Li Z-Y, Au L, Hartland GV, Li X et al (2006) Gold nanostructures: engineering their plasmonic properties for biomedical applications. Chem Soc Rev 35:1084–1094CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Schwartzberg AM, Olson TY, Talley CE, Zhang JZ (2006) Synthesis, characterization, and tunable optical properties of hollow gold nanospheres. J Phys Chem B 110:19935–19944CrossRefGoogle Scholar
  6. 6.
    Preciado-Flores S, Wang D, Wheeler DA, Newhouse R, Hensel JK, Schwartzberg A et al (2011) Highly reproducible synthesis of hollow gold nanospheres with near infrared surface plasmon absorption using PVP as stabilizing agent. J Mater Chem 21:2344–2350CrossRefGoogle Scholar
  7. 7.
    Wheeler DA, Newhouse RJ, Wang H, Zou S, Zhang JZ (2010) Optical properties and persistent spectral hole burning of near infrared-absorbing hollow gold nanospheres. J Phys Chem C 114:18126–18133CrossRefGoogle Scholar
  8. 8.
    Kim J, Xia M, Liu H (2005) Extinction coefficients of hemoglobin for near-infrared spectroscopy of tissue. Eng Med Biol Mag IEEE 24:118–121CrossRefGoogle Scholar
  9. 9.
    Lu W, Xiong CY, Zhang GD, Huang Q, Zhang R, Zhang JZ et al (2009) Targeted photothermal ablation of murine melanomas with melanocyte-stimulating hormone analog-conjugated hollow gold nanospheres. Clin Cancer Res 15:876–886CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Zhang JJ (2010) Biomedical applications of shape-controlled plasmonic nanostructures: a case study of hollow gold nanospheres for photothermal ablation therapy of cancer. J Phys Chem Lett 1:686–695CrossRefGoogle Scholar
  11. 11.
    Ji X, Shao R, Elliott AM, Stafford RJ, Esparza-Coss E, Bankson JA et al (2007) Bifunctional gold nanoshells with a superparamagnetic iron oxide-silica core suitable for both MR imaging and photothermal therapy. J Phys Chem C 111:6245–6251CrossRefGoogle Scholar
  12. 12.
    Melancon MP, Lu W, Yang Z, Zhang R, Cheng Z, Elliot AM et al (2008) In vitro and in vivo targeting of hollow gold nanoshells directed at epidermal growth factor receptor for photothermal ablation therapy. Mol Cancer Ther 7:1730–1739CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Wang J, Nantz M, Achilefu S, Kang KA (2011) Gold nanoparticle-fluorophore complex for conditionally fluorescing signal mediator. Anal Chim Acta 696:96–104CrossRefGoogle Scholar
  14. 14.
    Kang KA, Wang J, Jasinski B, Achilefu S (2011) Fluorescence manipulation by gold nanoparticles: from complete quenching to extensive enhancement. J Nanobiotechnol 9:16–29CrossRefGoogle Scholar
  15. 15.
    Wang J, O’Toole M, Massey A, Biswas S, Nantz M, Achilefu S et al (2011) Highly specific, NIR fluorescent contrast agent with emission controlled by gold nanoparticle. Adv Exp Med Biol 701:149–154CrossRefPubMedGoogle Scholar
  16. 16.
    Duchesne L, Gentili D, Comes-Franchini M, Fernig DG (2008) Robust ligand shells for biological applications of gold nanoparticles. Langmuir 24:13572–13580CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Jianting Wang
    • 1
  • Damon Wheeler
    • 2
  • Jin Z. Zhang
    • 2
  • Samuel Achilefu
    • 3
  • Kyung A. Kang
    • 1
  1. 1.Department of Chemical EngineeringUniversity of LouisvilleLouisvilleUSA
  2. 2.Department of Chemistry and BiochemistryUniversity of CaliforniaSanta CruzUSA
  3. 3.Department of RadiologyWashington University School of MedicineSt. LouisUSA

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