Polydopamine Nanoparticles as Label-Free Contrast Agents in Photoacoustic Imaging <i>In Vitro</i> and <i>In Vivo</i>

Polydopamine nanoparticles (PDNPs) are a class of nanomaterials formed by the self-polymerization of dopamine. They exhibit high biocompatibility, biodegradability, antioxidant properties, and ease of functionalization and can serve as photothermal agents when exposed to near-infrared (NIR) light. Another notable feature of PDNPs is their potential to act as contrast agents in photoacoustic imaging (PAI). In this technique, light absorption by endogenous chromophores or nanostructures induces thermal expansion, which generates sound waves that can be exploited to create images. Although PDNPs have shown promise as PAI contrast agents, their capabilities remain underexplored and insufficiently characterized in biological systems. This study presents the first comprehensive evaluation of PDNPs as PAI contrast agents. We investigated PDNPs of various sizes (∼150–1000 nm) and assessed their photoacoustic performance in diverse environments, including aqueous dispersions, ex vivo tissues, U87 cancer cell spheroids, fertilized quail eggs, and zebrafish embryos. Additionally, experimental results supported the development of a computational model to predict PDNP photoacoustic properties. Overall, this work highlights the significant, yet largely unexplored, potential of PDNPs as label-free PAI contrast agents, contributing to their future exploitation in clinical imaging.