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.
Subscribe to Journal
Get full journal access for 1 year
only $14.08 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
The data that support the plots within this paper and other findings of this study are available from the corresponding authors upon reasonable request.
Smith, A. M., Mancini, M. C. & Nie, S. Bioimaging: second window for in vivo imaging. Nat. Nanotechnol. 4, 710–711 (2009).
Homan, K. et al. Prospects of molecular photoacoustic imaging at 1064 nm wavelength. Opt. Lett. 35, 2663–2665 (2010).
Weber, J., Beard, P. C. & Bohndiek, S. E. Contrast agents for molecular photoacoustic imaging. Nat. Methods 13, 639–650 (2016).
Nie, L. M. & Chen, X. Y. Structural and functional photoacoustic molecular tomography aided by emerging contrast agents. Chem. Soc. Rev. 43, 7132–7170 (2014).
Jiang, Y. et al. Broadband absorbing semiconducting polymer nanoparticles for photoacoustic imaging in second near-infrared window. Nano Lett. 17, 4964–4969 (2017).
Ashraf, S. et al. in Light-Responsive Nanostructured Systems for Applications in Nanomedicine (ed. Sortino, S.) 169–202 (Springer International, Cham, 2016).
Li, W. W. & Chen, X. Y. Gold nanoparticles for photoacoustic imaging. Nanomedicine 10, 299–320 (2015).
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).
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).
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).
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).
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).
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).
Jia, H. et al. Synthesis of absorption-dominant small gold nanorods and their plasmonic properties. Langmuir 31, 7418–7426 (2015).
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).
Xu, X. et al. Seedless synthesis of high aspect ratio gold nanorods with high yield. J. Mater. Chem. A 2, 3528–3535 (2014).
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).
Thanh, N. T., Maclean, N. & Mahiddine, S. Mechanisms of nucleation and growth of nanoparticles in solution. Chem. Rev. 114, 7610–7630 (2014).
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).
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).
Qi, W. H. & Wang, M. P. Size and shape dependent melting temperature of metallic nanoparticles. Mater. Chem. Phys. 88, 280–284 (2004).
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).
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).
González-Rubio, G. et al. Femtosecond laser reshaping yields gold nanorods with ultranarrow surface plasmon resonances. Science 358, 640–644 (2017).
Wang, Y. & Dellago, C. Structural and morphological transitions in gold nanorods: a computer simulation study. J. Phys. Chem. B 107, 9214–9219 (2003).
Metwally, K., Mensah, S. & Baffou, G. Fluence threshold for photothermal bubble generation using plasmonic nanoparticles. J. Phys. Chem. C 119, 28586–28596 (2015).
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).
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).
Xu, M. & Wang, L. V. Photoacoustic imaging in biomedicine. Rev. Sci. Instrum. 77, 041101 (2006).
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).
Chen, Y.-S., Frey, W., Aglyamov, S. & Emelianov, S. Environment-dependent generation of photoacoustic waves from plasmonic nanoparticles. Small 8, 47–52 (2012).
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).
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).
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).
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).
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.
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.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
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
Journal of Colloid and Interface Science (2021)
A Redox-Responsive, In-Situ Polymerized Polyplatinum(IV)-Coated Gold Nanorod as An Amplifier of Tumor Accumulation for Enhanced Thermo-Chemotherapy
Localized surface plasmon resonance properties and biomedical applications of copper selenide nanomaterials
Materials Today Chemistry (2021)
Flash Scanning Volumetric Optoacoustic Tomography for High Resolution Whole‐Body Tracking of Nanoagent Kinetics and Biodistribution
Laser & Photonics Reviews (2021)
Advances in Colloid and Interface Science (2021)