Regulating Interparticle Proximity in Plasmonic Nanosphere Aggregates to Enhance Photoacoustic Response and Photothermal Stability

Designing plasmonic nanoparticles for biomedical photoacoustic (PA) imaging involves tailoring material properties at the nanometer scale. A key in developing plasmonic PA contrast nanoagents is to engineer their enhanced optical responses in the near‐infrared wavelength range, as well as heat transfer properties and photostability. This study introduces anisotropic plasmonic nanosphere aggregates with close interparticle proximity as photostable and efficient contrast agents for PA imaging. Silver (Ag) is particularly attractive because it has the strongest optical response and highest heat conductivity among plasmonic metals. The results demonstrate that close interparticle proximity in silver nanoaggregates (AgNAs), spatially confined within a polymer shell layer, leads to blackbody‐like optical absorption, resulting in robust PA signals through efficient pulsed heat generation and transfer. Additionally, the AgNAs exhibit a high photodamage threshold highlighting their potential to outperform conventional plasmonic contrast agents for high‐contrast PA imaging over multiple imaging sessions. Furthermore, the capability of the AgNAs are demonstrated for molecular PA cancer imaging in vivo by incorporating a tumor‐targeting peptide moiety. Anisotropic silver nanosphere aggregates with adjustable interparticle proximity have been developed to enhance photoacoustic signal. Close interparticle proximity within the silver nanoaggregates results in strong photoacoustic signal generation via efficient optical absorption and pulsed heat generation compared to more distant interparticle proximity within the nanoaggregates. Furthermore, the silver nanosphere aggregates exhibit a higher photodamage threshold than existing plasmonic photoacoustic contrast agents. The finding suggests an effective way to design photoacoustic contrast agents for high‐contrast photoacoustic imaging over multiple imaging sessions.