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Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 4, Iss. 11 — Nov. 1, 2013
  • pp: 2609–2618

Development and optimization of near-IR contrast agents for immune cell tracking

Pratixa P. Joshi, Soon Joon Yoon, Yun-Sheng Chen, Stanislav Emelianov, and Konstantin V. Sokolov  »View Author Affiliations

Biomedical Optics Express, Vol. 4, Issue 11, pp. 2609-2618 (2013)

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Gold nanorods (NRs) are attractive for in vivo imaging due to their high optical cross-sections and tunable absorbance. However, the feasibility of using NRs for cell tracking has not been fully explored. Here, we synthesized dye doped silica-coated NRs as multimodal contrast agents for imaging of macrophages – immune cells which play an important role in cancer and cardiovascular diseases. We showed the importance of silica coating in imaging of NR-labeled cells. Photoacoustic (PA) imaging of NRs labeled macrophages showed high sensitivity. Therefore, these results provide foundation for applications of silica-coated NRs and PA imaging in tracking of immune cells.

© 2013 Optical Society of America

OCIS Codes
(060.4230) Fiber optics and optical communications : Multiplexing
(170.0170) Medical optics and biotechnology : Medical optics and biotechnology
(170.2520) Medical optics and biotechnology : Fluorescence microscopy
(170.5120) Medical optics and biotechnology : Photoacoustic imaging
(170.2655) Medical optics and biotechnology : Functional monitoring and imaging
(160.4236) Materials : Nanomaterials

ToC Category:
Nanotechnology and Plasmonics

Original Manuscript: August 14, 2013
Revised Manuscript: September 30, 2013
Manuscript Accepted: October 21, 2013
Published: October 24, 2013

Pratixa P. Joshi, Soon Joon Yoon, Yun-Sheng Chen, Stanislav Emelianov, and Konstantin V. Sokolov, "Development and optimization of near-IR contrast agents for immune cell tracking," Biomed. Opt. Express 4, 2609-2618 (2013)

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  1. P. Jha, D. Golovko, S. Bains, D. Hostetter, R. Meier, M. F. Wendland, H. E. Daldrup-Link, “Monitoring of natural killer cell immunotherapy using noninvasive imaging modalities,” Cancer Res. 70(15), 6109–6113 (2010). [CrossRef] [PubMed]
  2. C. E. Green, T. Liu, V. Montel, G. Hsiao, R. D. Lester, S. Subramaniam, S. L. Gonias, R. L. Klemke, “Chemoattractant signaling between tumor cells and macrophages regulates cancer cell migration, metastasis and neovascularization,” PLoS ONE 4(8), e6713 (2009). [CrossRef] [PubMed]
  3. H. Hong, Y. Yang, Y. Zhang, W. Cai, “Non-invasive cell tracking in cancer and cancer therapy,” Curr. Top. Med. Chem. 10(12), 1237–1248 (2010). [CrossRef] [PubMed]
  4. I. F. Tannock, C. M. Lee, J. K. Tunggal, D. S. Cowan, M. J. Egorin, “Limited penetration of anticancer drugs through tumor tissue: A potential cause of resistance of solid tumors to chemotherapy,” Clin. Cancer Res. 8(3), 878–884 (2002). [PubMed]
  5. A. H. Kyle, L. A. Huxham, D. M. Yeoman, A. I. Minchinton, “Limited tissue penetration of taxanes: A mechanism for resistance in solid tumors,” Clin. Cancer Res. 13(9), 2804–2810 (2007). [CrossRef] [PubMed]
  6. M. R. Choi, K. J. Stanton-Maxey, J. K. Stanley, C. S. Levin, R. Bardhan, D. Akin, S. Badve, J. Sturgis, J. P. Robinson, R. Bashir, N. J. Halas, S. E. Clare, “A cellular Trojan Horse for delivery of therapeutic nanoparticles into tumors,” Nano Lett. 7(12), 3759–3765 (2007). [CrossRef] [PubMed]
  7. L. C. Kennedy, A. S. Bear, J. K. Young, N. A. Lewinski, J. Kim, A. E. Foster, R. A. Drezek, “T cells enhance gold nanoparticle delivery to tumors in vivo,” Nanoscale Res. Lett. 6(1), 283 (2011). [CrossRef] [PubMed]
  8. L. M. Ricles, S. Y. Nam, K. Sokolov, S. Y. Emelianov, L. J. Suggs, “Function of mesenchymal stem cells following loading of gold nanotracers,” Int. J. Nanomedicine 6, 407–416 (2011). [CrossRef] [PubMed]
  9. S. Y. Nam, L. M. Ricles, L. J. Suggs, S. Y. Emelianov, “In vivo ultrasound and photoacoustic monitoring of mesenchymal stem cells labeled with gold nanotracers,” PLoS ONE 7(5), e37267 (2012). [CrossRef] [PubMed]
  10. A. A. Oraevsky, A. A. Karabutov, S. V. Solomatin, E. V. Savateeva, V. A. Andreev, Z. Gatalica, H. Singh, R. D. Fleming, “Laser optoacoustic imaging of breast cancer in vivo,” Proc. SPIE 4256, 6–15 (2001). [CrossRef]
  11. X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, L. V. Wang, “Noninvasive laser-induced photoacoustic tomography for structural and functional in vivo imaging of the brain,” Nat. Biotechnol. 21(7), 803–806 (2003). [CrossRef] [PubMed]
  12. S. Mallidi, G. P. Luke, S. Emelianov, “Photoacoustic imaging in cancer detection, diagnosis, and treatment guidance,” Trends Biotechnol. 29(5), 213–221 (2011). [CrossRef] [PubMed]
  13. K. Sokolov, M. Follen, J. Aaron, I. Pavlova, A. Malpica, R. Lotan, R. Richards-Kortum, “Real-time vital optical imaging of precancer using anti-epidermal growth factor receptor antibodies conjugated to gold nanoparticles,” Cancer Res. 63(9), 1999–2004 (2003). [PubMed]
  14. B. M. Reinhard, M. Siu, H. Agarwal, A. P. Alivisatos, J. Liphardt, “Calibration of dynamic molecular rulers based on plasmon coupling between gold nanoparticles,” Nano Lett. 5(11), 2246–2252 (2005). [CrossRef] [PubMed]
  15. J. S. Aaron, N. Nitin, K. Travis, S. Kumar, T. Collier, S. Y. Park, M. José-Yacamán, L. Coghlan, M. Follen, R. Richards-Kortum, K. V. Sokolov, “Plasmon resonance coupling of metal nanoparticles for molecular imaging of carcinogenesis in vivo,” J. Biomed. Opt. 12(3), 034007 (2007). [CrossRef] [PubMed]
  16. S. Mallidi, T. Larson, J. Aaron, K. Sokolov, S. Emelianov, “Molecular specific optoacoustic imaging with plasmonic nanoparticles,” Opt. Express 15(11), 6583–6588 (2007). [CrossRef] [PubMed]
  17. M. C. Skala, M. J. Crow, A. Wax, J. A. Izatt, “Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres,” Nano Lett. 8(10), 3461–3467 (2008). [CrossRef] [PubMed]
  18. S. Mallidi, T. Larson, J. Tam, P. P. Joshi, A. Karpiouk, K. Sokolov, S. Emelianov, “Multiwavelength photoacoustic imaging and plasmon resonance coupling of gold nanoparticles for selective detection of cancer,” Nano Lett. 9(8), 2825–2831 (2009). [CrossRef] [PubMed]
  19. A. Wax, K. Sokolov, “Molecular imaging and darkfield microspectroscopy of live cells using gold plasmonic nanoparticles,” Laser Photon. Rev. 3(1-2), 146–158 (2009). [CrossRef]
  20. T. A. Larson, P. P. Joshi, K. Sokolov, “Preventing protein adsorption and macrophage uptake of gold nanoparticles via a hydrophobic shield,” ACS Nano 6(10), 9182–9190 (2012). [CrossRef] [PubMed]
  21. L. R. Hirsch, R. J. Stafford, J. A. Bankson, S. R. Sershen, B. Rivera, R. E. Price, J. D. Hazle, N. J. Halas, J. L. West, “Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance,” Proc. Natl. Acad. Sci. U.S.A. 100(23), 13549–13554 (2003). [CrossRef] [PubMed]
  22. C. Loo, A. Lin, L. Hirsch, M.-H. Lee, J. Barton, N. Halas, J. West, R. Drezek, “Nanoshell-enabled photonics-based imaging and therapy of cancer,” Technol. Cancer Res. Treat. 3(1), 33–40 (2004). [PubMed]
  23. J. M. Stern, J. Stanfield, W. Kabbani, J.-T. Hsieh, J. A. Cadeddu, “Selective prostate cancer thermal ablation with laser activated gold nanoshells,” J. Urol. 179(2), 748–753 (2008). [CrossRef] [PubMed]
  24. S. K. Baek, A. R. Makkouk, T. Krasieva, C. H. Sun, S. J. Madsen, H. Hirschberg, “Photothermal treatment of glioma; an in vitro study of macrophage-mediated delivery of gold nanoshells,” J. Neurooncol. 104(2), 439–448 (2011). [CrossRef] [PubMed]
  25. J. Chen, D. Wang, J. Xi, L. Au, A. Siekkinen, A. Warsen, Z.-Y. Li, H. Zhang, Y. Xia, X. Li, “Immuno gold nanocages with tailored optical properties for targeted photothermal destruction of cancer cells,” Nano Lett. 7(5), 1318–1322 (2007). [CrossRef] [PubMed]
  26. X. Yang, S. E. Skrabalak, Z. Y. Li, Y. Xia, L. V. Wang, “Photoacoustic tomography of a rat cerebral cortex in vivo with au nanocages as an optical contrast agent,” Nano Lett. 7(12), 3798–3802 (2007). [CrossRef] [PubMed]
  27. K. H. Song, C. Kim, C. M. Cobley, Y. Xia, L. V. Wang, “Near-infrared gold nanocages as a new class of tracers for photoacoustic sentinel lymph node mapping on a rat model,” Nano Lett. 9(1), 183–188 (2009). [CrossRef] [PubMed]
  28. Y. Xia, W. Li, C. M. Cobley, J. Chen, X. Xia, Q. Zhang, M. Yang, E. C. Cho, P. K. Brown, “Gold nanocages: From synthesis to theranostic applications,” Acc. Chem. Res. 44(10), 914–924 (2011). [CrossRef] [PubMed]
  29. H. Wang, T. B. Huff, D. A. Zweifel, W. He, P. S. Low, A. Wei, J.-X. Cheng, “In vitro and in vivo two-photon luminescence imaging of single gold nanorods,” Proc. Natl. Acad. Sci. U.S.A. 102(44), 15752–15756 (2005). [CrossRef] [PubMed]
  30. N. J. Durr, T. Larson, D. K. Smith, B. A. Korgel, K. Sokolov, A. Ben-Yakar, “Two-photon luminescence imaging of cancer cells using molecularly targeted gold nanorods,” Nano Lett. 7(4), 941–945 (2007). [CrossRef] [PubMed]
  31. N. Chanda, R. Shukla, K. V. Katti, R. Kannan, “Gastrin releasing protein receptor specific gold nanorods: breast and prostate tumor avid nanovectors for molecular imaging,” Nano Lett. 9(5), 1798–1805 (2009). [CrossRef] [PubMed]
  32. A. Wei, Q. Wei, and A. P. Leonov, “Gold nanorods as theranostic agents,” in Nanoplatform-based molecular imaging, X. Chen, ed. (John Wiley & Sons, Inc., 2011), pp. 659–681.
  33. C. L. Bayer, Y.-S. Chen, S. Kim, S. Mallidi, K. Sokolov, S. Emelianov, “Multiplex photoacoustic molecular imaging using targeted silica-coated gold nanorods,” Biomed. Opt. Express 2(7), 1828–1835 (2011). [CrossRef] [PubMed]
  34. J. V. Jokerst, M. Thangaraj, P. J. Kempen, R. Sinclair, S. S. Gambhir, “Photoacoustic imaging of mesenchymal stem cells in living mice via silica-coated gold nanorods,” ACS Nano 6(7), 5920–5930 (2012). [CrossRef] [PubMed]
  35. J. Choi, J. Yang, D. Bang, J. Park, J. S. Suh, Y. M. Huh, S. Haam, “Targetable gold nanorods for epithelial cancer therapy guided by near-ir absorption imaging,” Small 8(5), 746–753 (2012). [CrossRef] [PubMed]
  36. P. P. Joshi, S. J. Yoon, W. G. Hardin, S. Emelianov, K. V. Sokolov, “Conjugation of antibodies to gold nanorods through fc portion: Synthesis and molecular specific imaging,” Bioconjug. Chem. 24(6), 878–888 (2013). [CrossRef] [PubMed]
  37. T. P. Gustafson, Q. Cao, S. T. Wang, M. Y. Berezin, “Design of irreversible optical nanothermometers for thermal ablations,” Chem. Commun. (Camb.) 49(7), 680–682 (2012). [CrossRef] [PubMed]
  38. P. K. Jain, K. S. Lee, I. H. El-Sayed, M. A. El-Sayed, “Calculated absorption and scattering properties of gold nanoparticles of different size, shape, and composition: Applications in biological imaging and biomedicine,” J. Phys. Chem. B 110(14), 7238–7248 (2006). [CrossRef] [PubMed]
  39. C. Yu, J. Irudayaraj, “Multiplex biosensor using gold nanorods,” Anal. Chem. 79(2), 572–579 (2007). [CrossRef] [PubMed]
  40. A. Agarwal, S. W. Huang, M. O'Donnell, K. C. Day, M. Day, N. Kotov, S. Ashkenazi, “Targeted gold nanorod contrast agent for prostate cancer detection by photoacoustic imaging,” J. Appl. Phys. 102(6), 064701 (2007). [CrossRef]
  41. H. Cui, X. Yang, “In vivo imaging and treatment of solid tumor using integrated photoacoustic imaging and high intensity focused ultrasound system,” Med. Phys. 37(9), 4777–4781 (2010). [CrossRef] [PubMed]
  42. A. Taruttis, E. Herzog, D. Razansky, V. Ntziachristos, “Real-time imaging of cardiovascular dynamics and circulating gold nanorods with multispectral optoacoustic tomography,” Opt. Express 18(19), 19592–19602 (2010). [CrossRef] [PubMed]
  43. X. Huang, I. H. El-Sayed, W. Qian, M. A. El-Sayed, “Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods,” J. Am. Chem. Soc. 128(6), 2115–2120 (2006). [CrossRef] [PubMed]
  44. J. Shah, S. Park, S. Aglyamov, T. Larson, L. Ma, K. Sokolov, K. Johnston, T. E. Milner, S. Y. Emelianov, “Photoacoustic imaging and temperature measurement for photothermal cancer therapy,” J. Biomed. Opt. 13(3), 034024 (2008). [CrossRef] [PubMed]
  45. E. B. Dickerson, E. C. Dreaden, X. Huang, I. H. El-Sayed, H. Chu, S. Pushpanketh, J. F. McDonald, M. A. El-Sayed, “Gold nanorod assisted near-infrared plasmonic photothermal therapy (pptt) of squamous cell carcinoma in mice,” Cancer Lett. 269(1), 57–66 (2008). [CrossRef] [PubMed]
  46. F. Ratto, P. Matteini, S. Centi, F. Rossi, R. Pini, “Gold nanorods as new nanochromophores for photothermal therapies,” J Biophotonics 4(1-2), 64–73 (2011). [CrossRef] [PubMed]
  47. G. J. Nusz, S. M. Marinakos, A. C. Curry, A. Dahlin, F. Höök, A. Wax, A. Chilkoti, “Label-free plasmonic detection of biomolecular binding by a single gold nanorod,” Anal. Chem. 80(4), 984–989 (2008). [CrossRef] [PubMed]
  48. X. Huang, S. Neretina, M. A. El-Sayed, “Gold nanorods: From synthesis and properties to biological and biomedical applications,” Adv. Mater. 21(48), 4880–4910 (2009). [CrossRef]
  49. L. Tong, Q. Wei, A. Wei, J.-X. Cheng, “Gold nanorods as contrast agents for biological imaging: Optical properties, surface conjugation and photothermal effects,” Photochem. Photobiol. 85(1), 21–32 (2009). [CrossRef] [PubMed]
  50. M. M. Arnida, M. M. Janát-Amsbury, A. Ray, C. M. Peterson, H. Ghandehari, “Geometry and surface characteristics of gold nanoparticles influence their biodistribution and uptake by macrophages,” Eur. J. Pharm. Biopharm. 77(3), 417–423 (2011). [CrossRef] [PubMed]
  51. B. Nikoobakht, M. A. El-Sayed, “Preparation and growth mechanism of gold nanorods (nrs) using seed-mediated growth method,” Chem. Mater. 15(10), 1957–1962 (2003). [CrossRef]
  52. Y.-S. Chen, W. Frey, S. Kim, K. Homan, P. Kruizinga, K. Sokolov, S. Emelianov, “Enhanced thermal stability of silica-coated gold nanorods for photoacoustic imaging and image-guided therapy,” Opt. Express 18(9), 8867–8878 (2010). [CrossRef] [PubMed]
  53. H. Shi, X. He, K. Wang, Y. Yuan, K. Deng, J. Chen, W. Tan, “Rhodamine b isothiocyanate doped silica-coated fluorescent nanoparticles (rbitc-dsfnps)-based bioprobes conjugated to annexin v for apoptosis detection and imaging,” Nanomedicine 3(4), 266–272 (2007). [CrossRef] [PubMed]
  54. A. M. Alkilany, P. K. Nagaria, C. R. Hexel, T. J. Shaw, C. J. Murphy, M. D. Wyatt, “Cellular uptake and cytotoxicity of gold nanorods: Molecular origin of cytotoxicity and surface effects,” Small 5(6), 701–708 (2009). [CrossRef] [PubMed]
  55. R. Snyderman, M. C. Pike, D. G. Fischer, H. S. Koren, “Biologic and biochemical activities of continuous macrophage cell lines p388d1 and j774.1,” J. Immunol. 119(6), 2060–2066 (1977). [PubMed]
  56. R. Goldman, “Induction of a high phagocytic capability in p388d1, a macrophage-like tumor cell line, by 1 α, 25-dihydroxyvitamin d3,” Cancer Res. 44(1), 11–19 (1984). [PubMed]
  57. L. L. Chen, L. Jiang, Y. L. Wang, J. Qian, S. He, “Multilayered polyelectrolyte-coated gold nanorods as multifunctional optical contrast agents for cancer cell imaging,” J. Zhejiang Univ. Sci. B 11(6), 417–422 (2010). [CrossRef] [PubMed]
  58. A. K. Oyelere, P. C. Chen, X. Huang, I. H. El-Sayed, M. A. El-Sayed, “Peptide-conjugated gold nanorods for nuclear targeting,” Bioconjug. Chem. 18(5), 1490–1497 (2007). [CrossRef] [PubMed]
  59. H. Ding, K.-T. Yong, I. Roy, H. E. Pudavar, W. C. Law, E. J. Bergey, P. N. Prasad, “Gold nanorods coated with multilayer polyelectrolyte as contrast agents for multimodal imaging,” J. Phys. Chem. C 111(34), 12552–12557 (2007). [CrossRef]
  60. C. J. Murphy, A. M. Gole, J. W. Stone, P. N. Sisco, A. M. Alkilany, E. C. Goldsmith, S. C. Baxter, “Gold nanoparticles in biology: Beyond toxicity to cellular imaging,” Acc. Chem. Res. 41(12), 1721–1730 (2008). [CrossRef] [PubMed]
  61. C. Ungureanu, R. Kroes, W. Petersen, T. A. M. Groothuis, F. Ungureanu, H. Janssen, F. W. B. van Leeuwen, R. P. H. Kooyman, S. Manohar, T. G. van Leeuwen, “Light interactions with gold nanorods and cells: Implications for photothermal nanotherapeutics,” Nano Lett. 11(5), 1887–1894 (2011). [CrossRef] [PubMed]
  62. Y. S. Chen, W. Frey, S. Kim, P. Kruizinga, K. Homan, S. Emelianov, “Silica-coated gold nanorods as photoacoustic signal nanoamplifiers,” Nano Lett. 11(2), 348–354 (2011). [CrossRef] [PubMed]

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