Ultrasound imaging, with its substantial tissue penetration depth, safety, low cost and real-time imaging capability, is a widely-used imaging technique. However, poor contrast of soft tissues results in a low spatial resolution in the ultrasound images and decreases the diagnostic precision of this method. The gas-filled microbubbles can remarkably enhance the signal-to-noise ratio of the ultrasound images; however, microbubbles suffer from short circulation lifetimes and poor extravasation from the blood due to their large size. While better extravasation and pharmaceutical properties can be achieved by utilizing sub-micron sized contrast agents, these approaches provide limited contrast enhancement due to the lower acoustic scattering cross-sections. Here, we describe a distinct nanoscale ultrasound contrast platform using air-containing mesoporous nanoparticles (~100 nm diameter) with hydrophobic (octyl) functionalization. After suspension with Pluronic F127, the particles were stable in buffer and serum. While ordinarily mesoporous silica is hydrophilic, functionalization of the silica surface with octyl groups created pores that remained filled with air. When exposed to high intensity focused ultrasound (HIFU), these particles produced an observable ultrasound response, down to a particle concentration of 6× 10<sup>9</sup> particles mL<sup>-1</sup>, with no background signal and imaging could be sustained continuously for at least 20 minutes. Both the presence of the mesopores and their hydrophobic functionalization were found to be essential for obtaining contrast, but addition of only 0.5 v/v% ethanol quenched the ultrasound contrast dramatically. These studies supported the hypothesis that entrapped air could be pulled into bubble nuclei, which could then act as scatterers for ultrasound imaging. Finally, the particles could be lyophilized and reconstituted with no loss in contrast, and the particles showed very little hemolysis in whole blood, indicating their potential for blood pool imaging.

Hydrophobic mesoporous silica nanoparticles as fluorocarbon-free nanoscale ultrasound contrast agents

251st National Meeting (2016)

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