Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Miniature gold nanorods for photoacoustic molecular imaging in the second near-infrared optical window

An Author Correction to this article was published on 09 July 2019

This article has been updated

Abstract

In photoacoustic imaging, the second near-infrared (NIR-II) window is where tissue generates the least background signal. However, the large size of the few available contrast agents in this spectral range impedes their pharmacokinetics and decreases their thermal stability, leading to unreliable photoacoustic imaging. Here, we report the synthesis of miniaturized gold nanorods absorbing in the NIR-II that are 5–11 times smaller than regular-sized gold nanorods with a similar aspect ratio. Under nanosecond pulsed laser illumination, small nanorods are about 3 times more thermally stable and generate 3.5 times stronger photoacoustic signal than their absorption-matched larger counterparts. These unexpected findings are confirmed using theoretical and numerical analysis, showing that photoacoustic signal is not only proportional to the optical absorption of the nanoparticle solution but also to the surface-to-volume ratio of the nanoparticles. In living tumour-bearing mice, these small targeted nanorods display a 30% improvement in efficiency of agent delivery to tumours and generate 4.5 times greater photoacoustic contrast.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Synthesis procedure of small and large AuNRs and size characterization.
Fig. 2: Comparison of thermal stability of small and large AuNRs.
Fig. 3: Numerical analysis of photoacoustic signal generation from small and large AuNRs.
Fig. 4: Targeting specificity of small and large AuNRs for prostate cancer cells.
Fig. 5: Imaging of targeted small and large AuNRs in a murine model of prostate cancer.

Data availability

The data that support the plots within this paper and other findings of this study are available from the corresponding authors upon reasonable request.

Change history

  • 09 July 2019

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

  • 18 December 2019

    In the version of this Article originally published, the ORCID for Sanjiv S. Gambhir was incorrect; the correct ORCID is 0000-0002-2711-7554. This has now been amended.

References

  1. 1.

    Smith, A. M., Mancini, M. C. & Nie, S. Bioimaging: second window for in vivo imaging. Nat. Nanotechnol. 4, 710–711 (2009).

    CAS  Article  Google Scholar 

  2. 2.

    Homan, K. et al. Prospects of molecular photoacoustic imaging at 1064 nm wavelength. Opt. Lett. 35, 2663–2665 (2010).

    Article  Google Scholar 

  3. 3.

    Weber, J., Beard, P. C. & Bohndiek, S. E. Contrast agents for molecular photoacoustic imaging. Nat. Methods 13, 639–650 (2016).

    CAS  Article  Google Scholar 

  4. 4.

    Nie, L. M. & Chen, X. Y. Structural and functional photoacoustic molecular tomography aided by emerging contrast agents. Chem. Soc. Rev. 43, 7132–7170 (2014).

    CAS  Article  Google Scholar 

  5. 5.

    Jiang, Y. et al. Broadband absorbing semiconducting polymer nanoparticles for photoacoustic imaging in second near-infrared window. Nano Lett. 17, 4964–4969 (2017).

    CAS  Article  Google Scholar 

  6. 6.

    Ashraf, S. et al. in Light-Responsive Nanostructured Systems for Applications in Nanomedicine (ed. Sortino, S.) 169–202 (Springer International, Cham, 2016).

  7. 7.

    Li, W. W. & Chen, X. Y. Gold nanoparticles for photoacoustic imaging. Nanomedicine 10, 299–320 (2015).

    CAS  Article  Google Scholar 

  8. 8.

    Jana, N. R., Gearheart, L. & Murphy, C. J. Seed-mediated growth approach for shape-controlled synthesis of spheroidal and rod-like gold nanoparticles using a surfactant template. Adv. Mater. 13, 1389–1393 (2001).

    CAS  Article  Google Scholar 

  9. 9.

    Nikoobakht, B. & El-Sayed, M. A. Preparation and growth mechanism of gold nanorods (NRs) using seed-mediated growth method. Chem. Mater. 15, 1957–1962 (2003).

    CAS  Article  Google Scholar 

  10. 10.

    Vigderman, L. & Zubarev, E. R. High-yield synthesis of gold nanorods with longitudinal SPR peak greater than 1200 nm using hydroquinone as a reducing agent. Chem. Mater. 25, 1450–1457 (2013).

    CAS  Article  Google Scholar 

  11. 11.

    Wu, H.-Y., Chu, H.-C., Kuo, T.-J., Kuo, C.-L. & Huang, M. H. Seed-mediated synthesis of high aspect ratio gold nanorods with nitric acid. Chem. Mater. 17, 6447–6451 (2005).

    CAS  Article  Google Scholar 

  12. 12.

    Ali, M. R. K., Snyder, B. & El-Sayed, M. A. Synthesis and optical properties of small Au nanorods using a seedless growth technique. Langmuir 28, 9807–9815 (2012).

    CAS  Article  Google Scholar 

  13. 13.

    Song, J. et al. Ultrasmall gold nanorod vesicles with enhanced tumor accumulation and fast excretion from the body for cancer therapy. Adv. Mater. 27, 4910–4917 (2015).

    CAS  Article  Google Scholar 

  14. 14.

    Jia, H. et al. Synthesis of absorption-dominant small gold nanorods and their plasmonic properties. Langmuir 31, 7418–7426 (2015).

    CAS  Article  Google Scholar 

  15. 15.

    Li, Z. et al. Metabolizable small gold nanorods: size-dependent cytotoxicity, cell uptake and in vivo biodistribution. ACS Biomater. Sci. Eng. 2, 789–797 (2016).

    CAS  Article  Google Scholar 

  16. 16.

    Xu, X. et al. Seedless synthesis of high aspect ratio gold nanorods with high yield. J. Mater. Chem. A 2, 3528–3535 (2014).

    CAS  Article  Google Scholar 

  17. 17.

    Perrault, S. D., Walkey, C., Jennings, T., Fischer, H. C. & Chan, W. C. W. Mediating tumor targeting efficiency of nanoparticles through design. Nano Lett. 9, 1909–1915 (2009).

    CAS  Article  Google Scholar 

  18. 18.

    Thanh, N. T., Maclean, N. & Mahiddine, S. Mechanisms of nucleation and growth of nanoparticles in solution. Chem. Rev. 114, 7610–7630 (2014).

    CAS  Article  Google Scholar 

  19. 19.

    Bullen, C., Zijlstra, P., Bakker, E., Gu, M. & Raston, C. Chemical kinetics of gold nanorod growth in aqueous CTAB solutions. Cryst. Growth Design 11, 3375–3380 (2011).

    CAS  Article  Google Scholar 

  20. 20.

    Chen, Y.-S. et al. Enhanced thermal stability of silica-coated gold nanorods for photoacoustic imaging and image-guided therapy. Opt. Express 18, 8867–8878 (2010).

    CAS  Article  Google Scholar 

  21. 21.

    Qi, W. H. & Wang, M. P. Size and shape dependent melting temperature of metallic nanoparticles. Mater. Chem. Phys. 88, 280–284 (2004).

    CAS  Article  Google Scholar 

  22. 22.

    Zhu, J., Fu, Q., Xue, Y. & Cui, Z. Accurate thermodynamic relations of the melting temperature of nanocrystals with different shapes and pure theoretical calculation. Mater. Chem. Phys. 192, 22–28 (2017).

    CAS  Article  Google Scholar 

  23. 23.

    González-Rubio, G., Guerrero-Martínez, A. & Liz-Marzán, L. M. Reshaping, fragmentation, and assembly of gold nanoparticles assisted by pulse lasers. Acc. Chem. Res. 49, 678–686 (2016).

    Article  Google Scholar 

  24. 24.

    González-Rubio, G. et al. Femtosecond laser reshaping yields gold nanorods with ultranarrow surface plasmon resonances. Science 358, 640–644 (2017).

    Article  Google Scholar 

  25. 25.

    Wang, Y. & Dellago, C. Structural and morphological transitions in gold nanorods: a computer simulation study. J. Phys. Chem. B 107, 9214–9219 (2003).

    CAS  Article  Google Scholar 

  26. 26.

    Metwally, K., Mensah, S. & Baffou, G. Fluence threshold for photothermal bubble generation using plasmonic nanoparticles. J. Phys. Chem. C 119, 28586–28596 (2015).

    CAS  Article  Google Scholar 

  27. 27.

    Oraevsky, A. A., Jacques, S. L., Esenaliev, R. O. & Tittel, F. K. Laser-based optoacoustic imaging in biological tissues. Proc. SPIE 2134, 122–128 (1994).

    Google Scholar 

  28. 28.

    Cox, B. T. & Beard, P. C. Fast calculation of pulsed photoacoustic fields in fluids using k-space methods. J. Acoust. Soc. Am. 117, 3616–3627 (2005).

    CAS  Article  Google Scholar 

  29. 29.

    Xu, M. & Wang, L. V. Photoacoustic imaging in biomedicine. Rev. Sci. Instrum. 77, 041101 (2006).

    Article  Google Scholar 

  30. 30.

    Nguyen, S. C. et al. Study of heat transfer dynamics from gold nanorods to the environment via time-resolved infrared spectroscopy. ACS Nano 10, 2144–2151 (2016).

    CAS  Article  Google Scholar 

  31. 31.

    Chen, Y.-S., Frey, W., Aglyamov, S. & Emelianov, S. Environment-dependent generation of photoacoustic waves from plasmonic nanoparticles. Small 8, 47–52 (2012).

    CAS  Article  Google Scholar 

  32. 32.

    Cornelio, D. B., Roesler, R. & Schwartsmann, G. Gastrin-releasing peptide receptor as a molecular target in experimental anticancer therapy. Ann. Oncol. 18, 1457–1466 (2007).

    CAS  Article  Google Scholar 

  33. 33.

    Levi, J., Sathirachinda, A. & Gambhir, S. S. A high-affinity, high-stability photoacoustic agent for imaging gastrin-releasing peptide receptor in prostate cancer. Clin. Cancer Res. 20, 3721–3729 (2014).

    CAS  Article  Google Scholar 

  34. 34.

    Ischia, J., Patel, O., Bolton, D., Shulkes, A. & Baldwin, G. S. Expression and function of gastrin-releasing peptide (GRP) in normal and cancerous urological tissues. BJU Int. 113, 40–47 (2014).

    CAS  Article  Google Scholar 

  35. 35.

    Maddalena, M. E. et al. 177Lu-AMBA biodistribution, radiotherapeutic efficacy, imaging, and autoradiography in prostate cancer models with low GRP-R expression. J. Nucl. Med. 50, 2017–2024 (2009).

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported in part by grants from Breast Cancer Research Foundation under grant BCRF-16-043 and National Institutes of Health under grants CA158598 and CA149740 (to S.E.); and from NCI CCNE-T U54 CA199075, The Canary Foundation and The Sir Peter Michael Foundation (to S.S.G.). The authors acknowledge T. Stoyanova for providing the cells.

Author information

Affiliations

Authors

Contributions

Y.-S.C. and S.E. conceived the idea for the smaller AuNRs. Y.-S.C. and S.S.G. developed the ideas for prostate tumour targeting and the prostate tumour mouse models. Y.-S.C. performed the synthesis and characterization of the AuNRs, the in vitro experiments and the in vivo mouse experiments. Y.Z. performed the theoretical and numerical analysis. Y.-S.C. and S.J.Y. characterized the thermal stability of the AuNRs. S.E. and S.S.G. supervised the entire study. All authors contributed to the writing and editing of the manuscript.

Corresponding authors

Correspondence to Sanjiv Sam Gambhir or Stanislav Emelianov.

Ethics declarations

Competing interests

S.S.G. is co-founder, equity holder and board member of Endra Inc. that develops photoacoustic imaging strategies. The other authors declare no competing interests.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Materials, Supplementary Figures 1–10, Supplementary Tables 1–2

Reporting Summary

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Chen, YS., Zhao, Y., Yoon, S.J. et al. Miniature gold nanorods for photoacoustic molecular imaging in the second near-infrared optical window. Nat. Nanotechnol. 14, 465–472 (2019). https://doi.org/10.1038/s41565-019-0392-3

Download citation

Further reading

Search

Quick links

Find nanotechnology articles, nanomaterial data and patents all in one place. Visit Nano by Nature Research