Skip to main content
SpringerLink
Log in

A green synthesis of carbon nanoparticles from honey and their use in real-time photoacoustic imaging

  • Research Article
  • Published:
Nano Research Aims and scope Submit manuscript

Abstract

Imaging sentinel lymph nodes (SLN) could provide us with critical information about the progression of a cancerous disease. Real-time high-resolution intraoperative photoacoustic imaging (PAI) in conjunction with a near-infrared (NIR) probe may offer opportunities for the immediate imaging for direct identification and resection of SLN or collecting tissue samples. In this work a commercially amenable synthetic methodology is revealed for fabricating luminescent carbon nanoparticles with rapid clearance properties. A one-pot “green” technique is pursued, which involved rapid surface passivation of carbon nanoparticles with organic macromolecules (e.g., polysorbate, polyethyleneglycol) in solvent-free conditions. Interestingly, the naked carbon nanoparticles are derived for the first time, from commercial food grade honey. Surface coated particles are markedly smaller (∼7 nm) than previously explored particles (gold, single-walled carbon nanotubes, copper) for SLN imaging. The results indicate an exceptionally rapid signal enhancement (∼2 min) of the SLN. Owing to their strong optical absorption in the NIR region, tiny size and rapid lymphatic transport, this platform offers great potential for faster resection of SLN and may lower complications caused in axillary investigation by mismarking with dyes or low-resolution imaging techniques.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Wang, X. D.; Pang, Y. J.; Ku, G.; Xie, X. Y.; Stoica, G.; Wang, L. V. Noninvasive laser-induced photoacoustic tomography for structural and functional in vivo imaging of the brain. Nat. Biotechnol. 2003, 21, 803–806.

    Article  CAS  Google Scholar 

  2. Jokerst, J. V.; Thangaraj, M.; Kempen, P. J.; Sinclair, R.; Gambhir, S. S. Photoacoustic imaging of mesenchymal stem cells in living mice via silica-coated gold nanorods. ACS Nano. 2012, 6, 5920–5930.

    Article  CAS  Google Scholar 

  3. Wang, L. V.; Hu, S. Photoacoustic tomography: In vivo imaging from organelles to organs. Science 2012, 335, 1458–1462.

    Article  CAS  Google Scholar 

  4. Pan, D.; Pramanik, M.; Wickline, S. A.; Wang, L. V.; Lanza, G. M. Recent advances in colloidal gold nanobeacons for molecular photoacoustic imaging. Contrast Media Mol. Imaging 2011, 6, 378–388.

    Article  CAS  Google Scholar 

  5. Chen, Z. Y.; Ma, L. J.; Liu, Y.; Chen, C. Y. Applications of functionalized fullerenes in tumor theranostics. Theranostics 2012, 2, 238–250.

    Article  CAS  Google Scholar 

  6. de la Zerda, A.; Liu, Z.; Bodapati, S.; Teed, R.; Vaithilingam, S.; Khuri-Yakub, B. T.; Chen, X. Y.; Dai, H. J.; Gambhir, S. S. Ultrahigh sensitivity carbon nanotube agents for photoacoustic molecular imaging in living mice. Nano Lett. 2010, 10, 2168–72.

    Article  Google Scholar 

  7. Li, M. L.; Oh, J. T.; Xie, X.; Ku, G.; Wang, W.; Li, C.; Lungu, G.; Stoica, G.; Wang, L. V. Simultaneous molecular and hypoxia imaging of brain tumors in vivo using spectroscopic photoacoustic tomography. Proc. IEEE 2008, 96, 481–489.

    Article  CAS  Google Scholar 

  8. Wang, X. D.; Xie, X. Y.; Ku, G.; Wang, L. V.; Stoica, G. Noninvasive imaging of hemoglobin concentration and oxygenation in the rat brain using high-resolution photoacoustic tomography. J. Biomed. Opt. 2006, 11, 024015.

    Article  Google Scholar 

  9. Pan, D.; Pramanik, M.; Senpan, A.; Allen, J. S.; Zhang, H. Y.; Wickline, S. A.; Wang, L. V.; Lanza, G. M. Molecular photoacoustic imaging of angiogenesis with integrin-targeted gold nanobeacons. FASEB J. 2011, 25, 875–882.

    Article  CAS  Google Scholar 

  10. Pan, D.; Pramanik, M.; Senpan, A.; Ghosh, S.; Wickline, S. A.; Wang, L. V.; Lanza, G. M. Near infrared photoacoustic detection of sentinel lymph nodes with gold nanobeacons. Biomaterials 2010, 31, 4088–4093.

    Article  CAS  Google Scholar 

  11. Schneider, B. P.; Miller, K. D. Angiogenesis of breast cancer. J. Clin. Oncol. 2005, 23, 1782–1790.

    Article  CAS  Google Scholar 

  12. Agarwal, A.; Huang, S. W.; O’Donnell, M.; Day, K. C.; Day, M.; Kotov, N. A.; Ashkenazi, S. Targeted gold nanorod contrast agent for prostate cancer detection by photoacoustic imaging. J. Appl. Phys. 2007, 102, 064701.

    Article  Google Scholar 

  13. de la Zerda, A.; Zavaleta, C.; Keren, S.; Vaithilingam, S.; Bodapati, S.; Liu, Z.; Levi, J.; Smith, B. R.; Ma, T. J.; Oralkan, O.; Cheng, Z.; Chen, X. Y.; Dai, H. J.; Khuri-Yakub, B. T.; Gambhir, S. S. Carbon nanotubes as photoacoustic molecular imaging agents in living mice. Nat. Nanotechnol. 2008, 3, 557–562.

    Article  Google Scholar 

  14. Pan, D.; Cai, X.; Yalaz, C.; Senpan, A.; Omanakuttan, K.; Wickline, S. A.; Wang, L. V.; Lanza, G. M. Photoacoustic sentinel lymph node imaging with self-assembled copper neodecanoate nanoparticles. ACS Nano. 2012, 6, 1260–1267.

    Article  CAS  Google Scholar 

  15. Jose, J.; Grootendorst, D. J.; Vijn, T. W.; Wouters, M. W.; van Boven, H.; van Leeuwen, T. G.; Steenbergen, W.; Ruers, T. J. M.; Manohar, S. Initial results of imaging melanoma metastasis in resected human lymph nodes using photoacoustic computed tomography. J. Biomed. Opt. 2011, 16, 096021.

    Article  Google Scholar 

  16. Purushotham, A. D.; Upponi, S.; Klevesath, M. B.; Bobrow, L.; Millar, K.; Myles, J. P.; Duffy, S. W. Morbidity after sentinel lymph node biopsy in primary breast cancer: Results from a randomized controlled trial. J. Clin. Oncol. 2005, 23, 4312–4321.

    Article  Google Scholar 

  17. Krag, D. N.; Anderson, S. J.; Julian, T. B.; Brown, A. M.; Harlow, S. P.; Costantino, J. P.; Ashikaga, T.; Weaver, D. L.; Mamounas, E. P.; Jalovec, L. M. et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: Overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol. 2010, 11, 927–933.

    Article  Google Scholar 

  18. Krag, D.; Weaver, D.; Ashikaga, T.; Moffat, F.; Klimberg, V. S.; Shriver, C.; Feldman, S.; Kusminsky, R.; Gadd, M.; Kuhn, J. et al. The sentinel node in breast cancer-A multicenter validation study. N. Eng. J. Med. 1998, 339, 941–946.

    Article  CAS  Google Scholar 

  19. McMasters, K. M.; Tuttle, T. M.; Carlson, D. J. Sentinel lymph node biopsy for breast cancer: A suitable alternative to routine axillary dissection in multi-institutional practice when optimal technique is used. J. Clin. Oncol. 2000, 18, 2560–2566.

    CAS  Google Scholar 

  20. Zhang, H. F.; Maslov, K.; Stoica, G.; Wang, L. V. Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging. Nat. Biotechnol. 2006, 24, 848–851.

    Article  CAS  Google Scholar 

  21. Song, K. H.; Stein, E. W.; Margenthaler, J. A.; Wang, L. V. Noninvasive photoacoustic identification of sentinel lymph nodes containing methylene blue in vivo in a rat model. J. Biomed. Opt. 2008, 13, 054033.

    Article  Google Scholar 

  22. Li, P. C.; Wang, C. R. C.; Shieh, D. B.; Wei, C. W.; Liao, C. K.; Poe, C.; Jhan, S.; Ding, A. A.; Wu, Y. N. In vivo photoacoustic molecular imaging with simultaneous multiple selective targeting using antibody-conjugated gold nanorods. Opt. Express 2008, 16, 18605–18615.

    Article  CAS  Google Scholar 

  23. Wang, Z. J.; Wu, L. N.; Cai, W. Size-tunable synthesis of monodisperse water-soluble gold nanoparticles with high X-ray attenuation. Chem. Eur. J. 2010, 16, 1459–1463.

    Article  CAS  Google Scholar 

  24. Pramanik, M.; Swierczewska, M.; Green, D.; Sitharaman, V.; Wang, L. V. Single-walled carbon nanotubes as a multimodal-thermoacoustic and photoacoustic-contrast agent. J. Biomed. Opt. 2009, 14, 034018.

    Article  Google Scholar 

  25. de la Zerda, A.; Bodapati, S.; Teed, R.; May, S. Y.; Tabakman, S. M.; Liu, Z.; Khuri-Yakub, B. T.; Chen, X. Y.; Dai, H. J.; Gambhir, S. S. Family of enhanced photoacoustic imaging agents for high-sensitivity and multiplexing studies in living mice. ACS Nano 2012, 6, 4694–4701.

    Article  Google Scholar 

  26. Hu, Z. Y.; Pantoş, G. D.; Kuganathan, N.; Arrowsmith, R. L.; Jacobs, R. M. J.; Kociok-Köhn, G.; O’Byrne, J.; Jurkschat, K.; Burgos, P.; Tyrrell, R. M. et al. Interactions between amino acid-tagged naphthalenediimide and single walled carbon nanotubes for the design and construction of new bioimaging probes. Adv. Funct. Mater. 2012, 22, 503–518.

    Article  CAS  Google Scholar 

  27. Liu, Z.; Tabakman, S. M.; Chen, Z.; Dai, H. J. Preparation of carbon nanotube bioconjugates for biomedical applications. Nature Protoc. 2009, 4, 1372–1381.

    Article  CAS  Google Scholar 

  28. Sohrabnezhad, S.; Pourahmad, A.; Sadjadi, M. A. New methylene blue incorporated in mordenite zeolite as humidity sensor material. Mater. Lett. 2007, 61, 2311–2314.

    Article  CAS  Google Scholar 

  29. Xie, J.; Lee, S.; Chen, S. Y. Nanoparticle-based theranostic agents. Adv. Drug Deliv. Rev. 2010, 62, 1064–1079.

    Article  CAS  Google Scholar 

  30. Brewer, G. J. Copper toxicity in the general population. Clin. Neurophysiol. 2010, 121, 459–460.

    Article  Google Scholar 

  31. Schipper, M. L.; Nakayama-Ratchford, N.; Davis, C. R.; Kam, N. W. S.; Chu, P.; Liu, Z.; Sun, X. M.; Dai, H. J.; Gambhir, S. S. A pilot toxicology study of single-walled carbon nanotubes in a small sample of mice. Nat Nanotechnol. 2008, 3, 216–221.

    Article  CAS  Google Scholar 

  32. Yang, S. T.; Luo, J. B.; Zhou, Q. H.; Wang, H. F. Pharmacokinetics, metabolism and toxicity of carbon nanotubes for biomedical purposes. Theranostics 2012, 2, 271–282.

    Article  CAS  Google Scholar 

  33. Pan, D.; Cai, X.; Kim, B.; Stacy, A. J.; Wang, L. V.; Lanza, G. M. Rapid synthesis of near infrared polymeric micelles for real-time sentinel lymph node imaging. Adv. Healthcare Mater. 2012, 1, 582–589.

    Article  CAS  Google Scholar 

  34. Sun, Y. P.; Zhou, B.; Lin, Y.; Wang, W.; Fernando, K. A.; Pathak, P.; Meziani, M. J.; Harruff, B. A.; Wang, X.; Wang, H. F. et al. Quantum-sized carbon dots for bright and colorful photoluminescence. J. Am. Chem. Soc. 2006, 128, 7756–7757.

    Article  CAS  Google Scholar 

  35. Liu, H. P.; Ye, T.; Mao, C. D. Fluorescent carbon nanoparticles derived from candle soot. Angew. Chem., Int. Ed. 2007, 46, 6473–6475.

    Article  CAS  Google Scholar 

  36. Bourlinos, A. B.; Stassinopoulos, A.; Anglos, D.; Zboril, R.; Georgakilas, V.; Giannelis, E. P. Photoluminescent carbogenic dots. Chem. Mater. 2008, 20, 4539–4541.

    Article  CAS  Google Scholar 

  37. Huang, P.; Lin, J.; Wang, X. S.; Wang, Z.; Zhang, C. L.; He, M.; Wang, K.; Chen, F.; Li, Z. M.; Shen, G. X. et al. Light-triggered theranostics based on photosensitizer-conjugated carbon dots for simultaneous enhanced-fluorescence imaging and photodynamic therapy. Adv. Mater. 2012, 37, 5104–5110.

    Article  Google Scholar 

  38. Liu, Z.; Liang, X. J. Nano-carbons as theranostics. Theranostics 2012, 2, 235–237.

    Article  CAS  Google Scholar 

  39. Cao, L.; Yang, S. T.; Wang, X.; Luo, P. G.; Liu, J. H.; Sahu, S.; Liu, Y. M.; Sun, Y. P. Competitive performance of carbon “quantum” dots in optical bioimaging. Theranostics 2012, 2, 295–301.

    Article  CAS  Google Scholar 

  40. Swierczewska, M.; Choi, K. Y.; Mertz, E. L.; Huang, X. L.; Zhang, F.; Zhu, L.; Yoon, H. Y.; Park, J. H.; Bhirde, A.; Lee, S. et al. A facile, one-step nanocarbon functionalization for biomedical applications. Nano Lett. 2012, 12, 3613–3620.

    Article  CAS  Google Scholar 

  41. Zhu, Y.; Li, J.; Li, W. X.; Zhang, Y.; Yang, X. F.; Chen, N.; Sun, Y. H.; Zhao, Y.; Fan, C. H.; Huang, Q. The biocompatibility of nanodiamonds and their application in drug delivery systems. Theranostics 2012, 2, 302–312.

    Article  CAS  Google Scholar 

  42. Liu, Z.; Robinson, J. T.; Tabakman, S. M.; Yang, K.; Dai, H. J. Carbon materials for drug delivery and cancer therapy. Mater. Today 2011, 14, 316–323.

    Article  CAS  Google Scholar 

  43. Zhou, C.; Hao, G. Y.; Thomas, P.; Liu, J. B.; Yu, M. X.; Sun, S. S.; Öz, O. K.; Sun, X. K.; Zheng, J. Near infrared emitting radioactive gold nanoparticles with small-molecule-like pharmacokinetics. Angew. Chem., Int. Ed. 2012, 51, 10118–10122.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. C-TRAIN and Division of Cardiology, Washington University School of Medicine, 4320 Forest Park Avenue, Saint Louis, MO, 63108, USA

    Lina Wu, Allen J. Stacy, Micah Luderer, Gregory M. Lanza & Dipanjan Pan

  2. Key Laboratory of Molecular Imaging in College of Heilongjiang Province, Department of Radiology, the 4th Affiliated Hospital of Harbin Medical University, Harbin, 150001, China

    Lina Wu & Baozhong Shen

  3. Optical Imaging Laboratory, Department of Biomedical Engineering, Washington University in St. Louis, Campus Box 1097, One Brookings Drive, St. Louis, MO, 63130, USA

    Xin Cai, Wenxin Xing, Jun Xia, Ruiying Zhang & Lihong V. Wang

  4. Nano Research Facility (NNIN-NSF), Washington University in St. Louis, St. Louis, MO, 63130, USA

    Kate Nelson

Authors
  1. Lina Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xin Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kate Nelson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wenxin Xing
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jun Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ruiying Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Allen J. Stacy
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Micah Luderer
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Gregory M. Lanza
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Lihong V. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Baozhong Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Dipanjan Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Lihong V. Wang, Baozhong Shen or Dipanjan Pan.

Additional information

These authors contributed equally to this work

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wu, L., Cai, X., Nelson, K. et al. A green synthesis of carbon nanoparticles from honey and their use in real-time photoacoustic imaging. Nano Res. 6, 312–325 (2013). https://doi.org/10.1007/s12274-013-0308-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12274-013-0308-8

Keywords

Search

Navigation