Superfluorinated Extracellular Vesicles for In Vivo Imaging by 19F-MRI

Extracellula r vesicles (EVs) play a crucial role in cell-to-cell communication and have great potential as efficient delivery vectors. Howe v e r , a better understanding of EV in vivo behavior is hampered by the limitations of current imaging tools. In addition, chemical labels present the risk of altering the EV membrane features and, thus, in vivo behavior. 19F-MRI is a safe bioimaging technique providing selective images of exogenous probes. Here, we present the first example of fluorinated EVs containing PERFECTA, a branched molecule with 36 magnetically equivalent 19F atoms. A PERFECTA emulsion is g i v e n to the cells, and PERFECTA-containing EVs are naturally produced. PERFECTA-EVs maintain the physicochemical features, morphology, and biological fingerprint as native EVs but exhibit an intense 19F-NMR signal and excellent 19F relaxation times. In vivo 19F-MRI and tumor-targeting capabilities of stem cell-derived PERFECTA-EVs are also proved . We propose PERFECTA-EVs as promising biohybrids for imaging biodistribution and delivery of EVs throughout the body.

Automated summary

Extracellular vesicles (EVs) are important for cell-to-cell communication and show potential as efficient delivery vectors. However, current imaging tools have limitations in understanding EV behavior in vivo. This study presents the use of fluorinated EVs containing PERFECTA, a branched molecule with 36 magnetically equivalent 19F atoms, for imaging biodistribution and EV delivery. The PERFECTA-EVs maintained the characteristics and morphology of native EVs while exhibiting strong 19F-NMR signal and good 19F relaxation times.