Nano Research

, Volume 11, Issue 2, pp 676–685 | Cite as

Gold nanoshells: Contrast agents for cell imaging by cardiovascular optical coherence tomography

  • Jie Hu
  • Francisco Sanz-Rodríguez
  • Fernando Rivero
  • Emma Martín Rodríguez
  • Río Aguilar Torres
  • Dirk H. Ortgies
  • José García Solé
  • Fernando Alfonso
  • Daniel Jaque
Research Article


Optical coherence tomography (OCT) has gained considerable attention in interventional cardiovascular medicine and is currently used in clinical settings to assess atherosclerotic lesions and to optimize stent placement. Artery imaging at the cellular level constitutes the first step towards cardiovascular molecular imaging, which represents a major advance in the development of personalized noninvasive therapies. In this work, we demonstrate that cardiovascular OCT can be used to detect individual cells suspended in biocompatible fluids. Importantly, the combination of this catheter-based clinical technique with gold nanoshells (GNSs) as intracellular contrast agents led to a substantial enhancement in the backscattered signal produced by individual cells. This cellular contrast enhancement was attributed to the large backscattering cross-section of GNSs at the OCT laser wavelength (1,300 nm). A simple intensity analysis of OCT cross-sectional images of suspended cells makes it possible to identify the sub-population of living cells that successfully incorporated GNSs. The generalizability of this method was demonstrated using two different cell lines (HeLa and Jurkat cells). This work provides novel insights into cardiovascular molecular imaging using specifically modified GNSs.


OCT intravascular imaging gold nanoparticles 3D imaging 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.



This work is supported by the Spanish Ministry of Economy and Competitiveness under Project No. MAT2016-75362-C3-1-R and by Instituto de Salud Carlos III under Project No. PI16/00812. Jie Hu acknowledges the scholarship from the China Scholarship Council (No. 201506650003). Dirk H. Ortgies is grateful to the Spanish Ministry of Economy and Competitiveness for a Juan de la Cierva scholarship (No. FJCI-2014-21101).

Supplementary material

12274_2017_1674_MOESM1_ESM.pdf (1.2 mb)
Gold nanoshells: Contrast agents for cell imaging by cardiovascular optical coherence tomography


  1. [1]
    Fercher, A. F.; Drexler, W.; Hitzenberger, C. K.; Lasser, T. Optical coherence tomography-principles and applications. Rep. Prog. Phys. 2003, 66, 239–303.CrossRefGoogle Scholar
  2. [2]
    Alfonso, F.; Sandoval, J.; Cárdenas, A.; Medina, M.; Cuevas, C.; Gonzalo, N. Optical coherence tomography: From research to clinical application. Minerva Med. 2012, 103, 441–464.Google Scholar
  3. [3]
    Ashok, P. C.; Praveen, B. B.; Bellini, N.; Riches, A.; Dholakia, K.; Herrington, C. S. Multi-modal approach using Raman spectroscopy and optical coherence tomography for the discrimination of colonic adenocarcinoma from normal colon. Biomed. Opt. Express 2013, 4, 2179–2186.CrossRefGoogle Scholar
  4. [4]
    Fujimoto, J. G. Optical coherence tomography for ultrahigh resolution in vivo imaging. Nat. Biotechnol. 2003, 21, 1361–1367.CrossRefGoogle Scholar
  5. [5]
    Mattison, S. P.; Kim, W.; Park, J.; Applegate, B. E. Molecular imaging in optical coherence tomography. Curr. Mol. Imaging 2014, 3, 88–105.CrossRefGoogle Scholar
  6. [6]
    Zysk, A. M.; Nguyen, F. T.; Oldenburg, A. L.; Marks, D. L.; Boppart, S. A. Optical coherence tomography: A review of clinical development from bench to bedside. J. Biomed. Opt. 2007, 12, 051403.CrossRefGoogle Scholar
  7. [7]
    Bouma, B. E.; Yun, S.-H.; Vakoc, B. J.; Suter, M. J.; Tearney, G. J. Fourier-domain optical coherence tomography: Recent advances toward clinical utility. Curr. Opin. Biotechnol. 2009, 20, 111–118.CrossRefGoogle Scholar
  8. [8]
    Kennedy, B. F.; Kennedy, K. M.; Oldenburg, A. L.; Adie, S. G.; Boppart, S. A.; Sampson, D. D. Optical coherence elastography. In Optical Coherence Tomography: Technology and Applications. Drexler, W.; Fujimoto, J. G., Eds.; Springer International Publishing: Switzerland, 2015; pp1007–1054.CrossRefGoogle Scholar
  9. [9]
    Alfonso, F.; Dutary, J.; Paulo, M.; Gonzalo, N.; Pérez-Vizcayno, M. J.; Jiménez-Quevedo, P.; Escaned, J.; Bañuelos, C.; Hernández, R.; Macaya, C. Combined use of optical coherence tomography and intravascular ultrasound imaging in patients undergoing coronary interventions for stent thrombosis. Heart 2012, 98, 1213–1220.CrossRefGoogle Scholar
  10. [10]
    Bezerra, H. G.; Costa, M. A.; Guagliumi, G.; Rollins, A. M.; Simon, D. I. Intracoronary optical coherence tomography: A comprehensive review: Clinical and research applications. JACC: Cardiovasc. Interv. 2009, 2, 1035–1046.Google Scholar
  11. [11]
    Prati, F.; Stazi, F.; Dutary, J.; La Manna, A.; Di Giorgio, A.; Pawlosky, T.; Gonzalo, N.; Di Salvo, M. E.; Imola, F.; Tamburino, C. et al. Detection of very early stent healing after primary angioplasty: An optical coherence tomographic observational study of chromium cobaltum and first-generation drug-eluting stents. The detective study. Heart 2011, 97, 1841–1846.CrossRefGoogle Scholar
  12. [12]
    Rivero, F.; Bastante, T.; Cuesta, J.; Benedicto, A.; Restrepo, J. A.; Alfonso, F. Treatment of in-stent restenosis with bioresorbable vascular scaffolds: Optical coherence tomography insights. Can. J. Cardiol. 2015, 31, 255–259.CrossRefGoogle Scholar
  13. [13]
    Douma, K.; Prinzen, L.; Slaaf, D. W.; Reutelingsperger, C. P. M.; Biessen, E. A. L.; Hackeng, T. M.; Post, M. J.; van Zandvoort, M. A. M. J. Nanoparticles for optical molecular imaging of atherosclerosis. Small 2009, 5, 544–557.CrossRefGoogle Scholar
  14. [14]
    Chen, J. Y.; Saeki, F.; Wiley, B. J.; Cang, H.; Cobb, M. J.; Li, Z.-Y.; Au, L.; Zhang, H.; Kimmey, M. B.; Li, X. D. et al. Gold nanocages: Bioconjugation and their potential use as optical imaging contrast agents. Nano Lett. 2005, 5, 473–477.CrossRefGoogle Scholar
  15. [15]
    Bibikova, O.; Popov, A.; Bykov, A.; Prilepskii, A.; Kinnunen, M.; Kordas, K.; Bogatyrev, V.; Khlebtsov, N.; Vainio, S.; Tuchin, V. Optical properties of plasmon-resonant bare and silica-coated nanostars used for cell imaging. J. Biomed. Opt. 2015, 20, 076017.CrossRefGoogle Scholar
  16. [16]
    Skrabalak, S. E.; Chen, J.; Au, L.; Lu, X.; Li, X.; Xia, Y. Gold nanocages for biomedical applications. Adv. Mater. 2007, 19, 3177–3184.CrossRefGoogle Scholar
  17. [17]
    Gobin, A. M.; Lee, M. H.; Halas, N. J.; James, W. D.; Drezek, R. A.; West, J. L. Near-infrared resonant nanoshells for combined optical imaging and photothermal cancer therapy. Nano Lett. 2007, 7, 1929–1934.CrossRefGoogle Scholar
  18. [18]
    Hu, J.; Rivero, F.; Torres, R. A.; Ramírez, H. L.; Rodríguez, E. M.; Alfonso, F.; Solé, J. G.; Jaque, D. Dynamic single gold nanoparticle visualization by clinical intracoronary optical coherence tomography. J. Biophotonics 2017, 10, 674–682.CrossRefGoogle Scholar
  19. [19]
    Skala, M. C.; Crow, M. J.; Wax, A.; Izatt, J. A. Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres. Nano Lett. 2008, 8, 3461–3467.CrossRefGoogle Scholar
  20. [20]
    Loo, C.; Lowery, A.; Halas, N.; West, J.; Drezek, R. Immunotargeted nanoshells for integrated cancer imaging and therapy. Nano Lett. 2005, 5, 709–711.CrossRefGoogle Scholar
  21. [21]
    De León, Y. P.; Pichardo-Molina, J. L.; Ochoa, N. A.; Luna-Moreno, D. Contrast enhancement of optical coherence tomography images using branched gold nanoparticles. J. Nanomater. 2012, 2012, 571015.Google Scholar
  22. [22]
    De La Zerda, A.; Prabhulkar, S.; Perez, V. L.; Ruggeri, M.; Paranjape, A. S.; Habte, F.; Gambhir, S. S.; Awdeh, R. M. Optical coherence contrast imaging using gold nanorods in living mice eyes. Clin. Exp. Ophthalmol. 2015, 43, 358–366.CrossRefGoogle Scholar
  23. [23]
    Adler, D. C.; Huang, S.-W.; Huber, R.; Fujimoto, J. G. Photothermal detection of gold nanoparticles using phasesensitive optical coherence tomography. Opt. Express 2008, 16, 4376–4393.CrossRefGoogle Scholar
  24. [24]
    Fratoddi, I.; Venditti, I.; Cametti, C.; Russo, M. V. How toxic are gold nanoparticles? The state-of-the-art. Nano Res. 2015, 8, 1771–1799.CrossRefGoogle Scholar
  25. [25]
    Masters, J. R. HeLa cells 50 years on: The good, the bad and the ugly. Nat. Rev. Cancer 2002, 2, 315–319.CrossRefGoogle Scholar
  26. [26]
    Mosmann, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods 1983, 65, 55–63.CrossRefGoogle Scholar
  27. [27]
    Li, M.; Lohmüller, T.; Feldmann, J. Optical injection of gold nanoparticles into living cells. Nano Lett. 2015, 15, 770–775.CrossRefGoogle Scholar
  28. [28]
    Cui, Y.; Wang, X. L.; Ren, W.; Liu, J.; Irudayaraj, J. Optical clearing delivers ultrasensitive hyperspectral dark-field imaging for single-cell evaluation. ACS Nano 2016, 10, 3132–3143.CrossRefGoogle Scholar
  29. [29]
    Wax, A.; Sokolov, K. Molecular imaging and darkfield microspectroscopy of live cells using gold plasmonic nanoparticles. Laser Photonics Rev. 2009, 3, 146–158.CrossRefGoogle Scholar
  30. [30]
    Qian, W.; Huang, X. H.; Kang, B.; El-Sayed, M. A. Dark-field light scattering imaging of living cancer cell component from birth through division using bioconjugated gold nanoprobes. J. Biomed. Opt. 2010, 15, 046025.CrossRefGoogle Scholar
  31. [31]
    Jaque, D.; Maestro, L. M.; del Rosal, B.; Haro-Gonzalez, P.; Benayas, A.; Plaza, J. L.; Rodríguez, E. M.; Solé, J. G. Nanoparticles for photothermal therapies. Nanoscale 2014, 6, 9494–9530.CrossRefGoogle Scholar

Copyright information

© Tsinghua University Press and Springer-Verlag GmbH Germany 2018

Authors and Affiliations

  • Jie Hu
    • 1
  • Francisco Sanz-Rodríguez
    • 1
    • 2
    • 3
  • Fernando Rivero
    • 4
  • Emma Martín Rodríguez
    • 1
    • 2
  • Río Aguilar Torres
    • 4
  • Dirk H. Ortgies
    • 1
    • 2
  • José García Solé
    • 1
  • Fernando Alfonso
    • 4
  • Daniel Jaque
    • 1
    • 2
  1. 1.Fluorescence Imaging Group, Departamento de Física de Materiales, Instituto Nicolás Cabrera, Facultad de CienciasUniversidad Autónoma de MadridMadridSpain
  2. 2.Instituto Ramón y Cajal de Investigación SanitariaHospital Ramón y CajalMadridSpain
  3. 3.Departamento de BiologíaUniversidad Autónoma de MadridMadridSpain
  4. 4.Cardiology DepartmentHospital Universitario de la Princesa, IIS-IP, Universidad Autónoma de MadridMadridSpain

Personalised recommendations