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.
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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.
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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.
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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.
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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.
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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
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DOI: https://doi.org/10.1038/s41565-019-0392-3
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