Exploring the structure-property relationships of ultrasonic/MRI dual imaging magnetite/PLA microbubbles: magnetite@Cavity versus magnetite@Shell systems

Two types of magnetite/PLA composite microbubbles with different magnetite loading sites (magnetite nanoparticles [MNPs] were loaded in shell or core part), named as Fe3O4@Shell and Fe3O4@Cavity microbubbles, were respectively fabricated by an improved W-1/O/W-2 double emulsification approach and by an interfacial coprecipitation joint double emulsification approach. The preparation parameters were crucial factors for controlling the morphologies and structures of the microbubbles. To clarify the relationship between their structural characteristics and their properties, the T (2)-weighted magnetic resonance imaging (MRI) capabilities as well as the sound attenuation behavior of the microbubbles were investigated. The results demonstrate that the encapsulation of MNPs in either the inner cavity or the shell provides improved sound attenuation, the two types of microbubbles provide comparable sound attenuation enhancement properties, whereas Fe3O4@Shell microbubbles exhibit better T (2)-weighted MRI capabilities. The T (2) relaxation time decreased from 219.5 to 62.1 ms for the Fe3O4@Cavity microbubbles and from 163.8 to 45.7 ms for the Fe3O4@Shell microbubbles, as the iron concentration increased from 0.05 to 1 mM. In addition, both types of microbubbles exhibit no cytotoxicity to either NRK or BRL-3A metabolic cell cultures. These results suggest that these magnetite-containing microbubbles have great potential as ultrasonic/MR dual contrast imaging agents.