Structural engineering of silver nanoparticles for enhanced photoacoustic imaging

Photoacoustic (PA) imaging is a diagnostic tool widely explored in (pre)clinical settings, as it combines the strengths of optical and ultrasound imaging, resulting in high contrast resolution and deep tissue penetration. Although PA imaging can directly visualize some endogenous molecules (e.g. deoxygenated and oxygenated hemoglobin), most of its applications require the administration of external probes, including organic dyes and inorganic nanoparticles. Despite being historically used for antimicrobial and wound healing applications, silver nanoparticles (AgNPs) possess clear merits for PA imaging, including tunable optical properties, high-quality localized surface plasmon (LSP) resonances, strong photothermal conversions, and photostability. In this study, we explored new PA imaging probes based on silver nanocores (with different morphologies and sizes) and polymer shells, and identified the structural features that provide improved biocompatibility, stability, and probe performance. Notably, the size and morphology of the cores strongly impacted the PA signal of the silver probes. For example, among the different particles tested, plate-shaped AgNPs generated up to 3-fold greater signal, as their optical properties, specifically LSP bands and extinction coefficients, were better suited for PA imaging. Even if nanoconstructs displayed apparent inadequate optical features, e.g. in the case of spherical AgNPs with LSP bands centered in the blue region of the spectrum, a strong PA signal could still be obtained by manipulating the core size, resulting in up to 2-fold greater signal for larger particles in comparison to their smaller counterparts. All AgNPs were stable in biological environments, did not photobleach, and preserved strong PA imaging signals in ex vivo setups. Taken together, our results exemplify the merits of AgNPs as PA imaging agents, providing a better understanding of the nanoengineering of new imaging probes and thereby extending the applications of AgNPs beyond traditional antimicrobial and wound healing applications. Since some of the nanoconstructs we explored in this study are currently being investigated as photothermal agents in clinical trials, new opportunities may arise in intraoperative imaging and image-guided therapy.