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

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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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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.

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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.

Author information

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.

Correspondence to Sanjiv Sam Gambhir or Stanislav Emelianov.

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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.

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