Silver nanoparticle-embedded microbubble as a dual-mode ultrasound and optical imaging probe

Microbubbles (MBs) coupled with nanoparticles represent a new class of multifunctional probe for multiscale biomedical imaging and drug delivery. In this study, we describe the development of multifunctional, microscale microbubble probes that are composed of a nitrogen gas core and a biocompatible polymer shell harboring silver nanoparticles (AgNPs). Ultrasound imaging studies show that the presence of AgNPs in the MB significantly improves the contrast of ultrasound images. The AgNPs within individual MB can be also imaged by using dark-field microscopy (DFM), which suggests that AgNPs in the polymer shell adopt multiple structural forms. AgNPs are released from the polymer shell following a brief exposure to an ultrasonic field and are subsequently taken up by living cells. AgNPs within labeled cells are imaged by DFM, while surface-enhanced Raman scattering is used to identify specific cytoplasmic biomolecules that bind to the surface of the AgNP. Collectively, these studies demonstrate the application of multifunctional MBs for micrometer scale contrast-enhanced ultrasound imaging, as vehicles for the ultrasound-based delivery of optical probes and drugs to cells, and for imaging of chemical sensing of individual nanopartiles within cells and tissue.