(G-251) Compact silver nanosphere aggregates for photoacoustic imaging with high imaging contrast

Introduction:: Photoacoustic (PA) imaging is capable of visualizing optical absorption with high resolution and depth beyond ballistic propagation of photons. Exogenous contrast agents that exhibit distinctive optical spectra compared to endogenous molecules can enhance PA contrast and enable non-invasive detection of specific molecular or cellular events of interest in vivo. To achieve contrast-enhanced PA imaging, exogenous contrast agents must have desired optical absorption, heat transfer, and photostability. Plasmonic nanoparticles (NPs) are of particular interest as exogenous contrast agents due to their geometry-dependent tunable optical properties and high heat conductivity. While existing plasmonic contrast agents with high aspect ratios, such as gold nanorods, exhibit strong PA signals and contrast, their poor photodamage threshold below a typical laser intensity used in PA imaging (10 mJ/cm²) impedes imaging applications. Here, we developed anisotropic silver nanosphere aggregates (AgNAs) with strong PA responses and a high photodamage threshold for high imaging contrast and imaging stability. We showed the applicability of AgNAs for PA imaging in vivo.


Materials and Methods:: AgNAs were synthesized via a seed-mediated growth of gold seeds confined in an ellipsoid nanoscopic space (Fig. 1A). The NP structure, optical characteristics, and PA responses were characterized using transmission electron microscopy (TEM), UV-vis-NIR spectroscopy, and US/PA imaging (Vevo LAZR, 20 MHz, 680-900 nm). For in vivo studies, AgNAs were intravenously injected into mice, and the spleen was imaged at multiple time points (0, 0.5, 3, and 24 hours) across 700-900 nm wavelengths.


Results, Conclusions, and Discussions:: Results and Discussion: Anisotropic AgNAs were created via template-mediated growth method. Increasing Ag precursors in the growth step led to larger diameters and closer inter-sphere spacing of AgNSs, resulting in closer proximity between nearby AgNSs (Fig. 1B). The closer proximity induced stronger plasmon coupling, leading to the increased absorption intensity (Fig. 1C). Therefore, AgNAs exhibited higher PA signals (Fig. 1D). Furthermore, the close proximity-AgNAs generated stable PA signals at a laser fluence of 20 mJ/cm² for 1,000 pulses without any structural damage (Figs. 1E, 1F). The high photostability of the AgNAs showed their potential for sustained PA imaging. Finally, we validated in vivo PA imaging capabilities via monitoring of the AgNAs in a scenario of systemic delivery; specifically, accumulation of AgNAs at the spleen. After systemic injections of AgNAs into mice, PA signals and imaging contrast gradually increased at the spleen over 24 hours (Figs. 1G, H). Results collectively confirmed that AgNAs can be used as a contrast agent for PA imaging with high imaging contrast and imaging stability.

Conclusion: We designed anisotropic AgNAs with strong PA responses and high photodamage threshold to achieve PA imaging with high imaging contrast and imaging stability. Results showed that close proximity nanospheres in AgNAs resulted in increased optical absorption, thereby producing high PA signals and imaging contrast. Furthermore, our AgNAs exhibited excellent photostability. After systemic administration, we successfully validated our AgNAs as a contrast agent for in vivo PA imaging. In the future, we plan to investigate whether our AgNAs can be disassembled into small singular AgNSs, thereby minimizing any potential biocompatibility concerns associated with remaining plasmonic NPs.




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