Multicore liquid perfluorocarbon-loaded multimodal nanoparticles for stable ultrasound and 19 F MRI applied to in vivo cell tracking

Olga Koshkina, Guillaume Lajoinie, Francesca Baldelli Bombelli, Edyta Swider, Luis J. Cruz, Paul B. White, Ralf Schweins, Yusuf Dolen, Eric A.W. van Dinther, N. Koen van Riessen, Sarah E. Rogers, Remco Fokkink, Ilja K. Voets, Ernst R.H. van Eck, Arend Heerschap, Michel Versluis, Chris L. de Korte, Carl G. Figdor, I. Jolanda M. de Vries, Mangala Srinivas (Corresponding author)

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Abstract

Ultrasound is the most commonly used clinical imaging modality. However, in applications requiring cell-labeling, the large size and short active lifetime of ultrasound contrast agents limit their longitudinal use. Here, 100 nm radius, clinically applicable, polymeric nanoparticles containing a liquid perfluorocarbon, which enhance ultrasound contrast during repeated ultrasound imaging over the course of at least 48 h, are described. The perfluorocarbon enables monitoring the nanoparticles with quantitative 19 F magnetic resonance imaging, making these particles effective multimodal imaging agents. Unlike typical core–shell perfluorocarbon-based ultrasound contrast agents, these nanoparticles have an atypical fractal internal structure. The nonvaporizing highly hydrophobic perfluorocarbon forms multiple cores within the polymeric matrix and is, surprisingly, hydrated with water, as determined from small-angle neutron scattering and nuclear magnetic resonance spectroscopy. Finally, the nanoparticles are used to image therapeutic dendritic cells with ultrasound in vivo, as well as with 19 F MRI and fluorescence imaging, demonstrating their potential for long-term in vivo multimodal imaging.

Original languageEnglish
Article number1806485
Number of pages14
JournalAdvanced Functional Materials
Volume29
Issue number19
DOIs
Publication statusPublished - 9 May 2019

Keywords

  • F MRI
  • cell therapy
  • cell tracking
  • multimodal imaging
  • perfluorocarbons
  • ultrasound
  • F-19 MRI

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    Koshkina, O., Lajoinie, G., Baldelli Bombelli, F., Swider, E., Cruz, L. J., White, P. B., Schweins, R., Dolen, Y., van Dinther, E. A. W., van Riessen, N. K., Rogers, S. E., Fokkink, R., Voets, I. K., van Eck, E. R. H., Heerschap, A., Versluis, M., de Korte, C. L., Figdor, C. G., de Vries, I. J. M., & Srinivas, M. (2019). Multicore liquid perfluorocarbon-loaded multimodal nanoparticles for stable ultrasound and 19 F MRI applied to in vivo cell tracking. Advanced Functional Materials, 29(19), [1806485]. https://doi.org/10.1002/adfm.201806485