Novel Magnetic Elastic Phase-Change Nanodroplets as Dual Mode Contrast Agent for Ultrasound and Magnetic Resonance Imaging

Recently, dual-mode imaging systems merging magnetic resonance imaging (MRI) and ultrasound (US) have been developed. Designing a dual-mode contrast agent is complex due to different mechanisms of enhancement. Herein, we describe novel phase change nanodroplets (PCNDs) with perfluoropentane encapsulated in a pre-polyglycerol sebacate (pre-PGS) shell loaded with polyethylene glycol (PEG)-coated iron oxide nanoparticles as having a dual-mode contrast agent effect. Iron oxide nanoparticles were prepared via the chemical co-precipitation method and PCNDs were prepared via the solvent displacement technique. PCNDs showed excellent enhancement in the in vitro US much more than Sonovue (R) microbubbles. Furthermore, they caused a susceptibility effect resulting in a reduction of signal intensity on MRI. An increase in the concentration of nanoparticles caused an increase in the MR contrast effect but a reduction in US intensity. The concentration of nanoparticles in a shell of PCNDs was optimized to obtain a dual-mode contrast effect. Biocompatibility, hemocompatibility, and immunogenicity assays showed that PCNDs were safe and non-immunogenic. Another finding was the dual-mode potential of unloaded PCNDs as T1 MR and US contrast agents. Results suggest the excellent potential of these PCNDs for use as dual-mode contrast agents for both MRI and US.