Iron oxide nanoparticle-containing microbubble composites as contrast agents for MR and ultrasound dual-modality imaging.

Abstract

Magnetic resonance (MR) and ultrasound (US) imaging are widely used diagnostic modalities for various experimental and clinical applications. In this study, iron oxide nanoparticle-embedded polymeric microbubbles were designed as multi-modal contrast agents for hybrid MR-US imaging. These magnetic nano-in-micro imaging probes were prepared via a one-pot emulsion polymerization to form poly(butyl cyanoacrylate) microbubbles, along with the oil-in-water (O/W) encapsulation of iron oxide nanoparticles in the bubble shell. The nano-in-micro embedding strategy was validated using NMR and electron microscopy. These hybrid imaging agents exhibited strong contrast in US and an increased transversal relaxation rate in MR. Moreover, a significant increase in longitudinal and transversal relaxivities was observed after US-induced bubble destruction, which demonstrated triggerable MR imaging properties. Proof-of-principle in vivo experiments confirmed that these nanoparticle-embedded microbubble composites are suitable contrast agents for both MR and US imaging. In summary, these magnetic nano-in-micro hybrid materials are highly interesting systems for bimodal MR-US imaging, and their enhanced relaxivities upon US-induced destruction recommend them as potential vehicles for MR-guided US-mediated drug and gene delivery.