Enhanced photoacoustic response with plasmonic nanoparticle-templated microbubbles

We report a versatile approach for the generation of novel nanoparticle-templated microbubbles capable of simultaneous contrast enhancement in both ultrasound and photoacoustic imaging. Fabrication of the dual modality contrast agent relies on specific binding of avidinated gold nanoparticles to a biotinylated microbubble shell, providing stoichiometric control over nanoparticle surface density and optical absorption, while still retaining the essential acoustic properties of the microbubble. Nanoparticle laden microbubbles were shown to be exceptionally efficient photoacoustic agents, with an enhanced photoacoustic response compared to free nanoparticles or unconjugated mixtures of nanoparticles and microbubbles. Upon destruction of the microbubble gas core, a marked reduction in photoacoustic signal amplitude was observed, demonstrating the importance of placing the nanoparticles onto a compressible gas core in achieving the photoacoustic enhancement. We further demonstrate dual modality contrast enhanced photoacoustic and ultrasound imaging in a flow-through tissue phantom. Our results show that nanoparticle-templated microbubbles are promising for imaging, biosensing and theranostic applications.