Pivotal role of the protein corona in the cell uptake of fluorinated nanoparticles with increased sensitivity for F-19-MR imaging

In vivo cell tracking by non-invasive imaging technologies is needed to accelerate the clinical translation of innovative cell-based therapies. In this regard, F-19-MRI has recently gained increased attention for unbiased localization of labeled cells over time. To push forward the use of F-19-MRI for cell tracking, the development of highly performant F-19-probes is required. PLGA-based NPs containing PERFECTA, a multibranched superfluorinated molecule with an optimal MRI profile thanks to its 36 magnetically equivalent fluorine atoms, are promising F-19-MRI probes. In this work we demonstrate the importance of the surface functionalization of these NPs in relation to their interaction with the biological environment, stressing the pivotal role of the formation of the protein corona (PC) in their cellular labelling efficacy. In particular, our studies showed that the formation of PC NPs strongly promotes the cellular internalization of these NPs in microglia cells. We advocate that the formation of PC NPs in the culture medium can be a key element to be used for the optimization of cell labelling with a considerable increase of the detection sensitivity by F-19-MRI.

Automated summary

Non-invasive imaging technologies are crucial for tracking cells in vivo and accelerating the clinical translation of cell-based therapies. F-19-MRI has gained attention for unbiased cell localization, but the development of high-performance F-19-probes is necessary. This study highlights the importance of surface functionalization of PLGA-based NPs containing PERFECTA, emphasizing the role of protein corona formation in enhancing cellular labeling efficacy. The formation of protein corona in culture medium can significantly increase the detection sensitivity by F-19-MRI.