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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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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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.
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