19F magnetic resonance imaging (MRI) using fluoropolymer tracers has recently emerged as a promising, noninvasive diagnostic tool in modern medicine. However, despite its potential, 19F MRI remains overlooked and underused due to the limited availability or unfavorable properties of fluorinated tracers. Herein, we report a straightforward synthetic route to highly fluorinated 19F MRI nanotracers via aqueous dispersion polymerization- induced self-assembly of a water-soluble fluorinated monomer. A polyethylene glycol-based macromolecular chaintransfer agent was extended by RAFT-mediated N-(2,2,2- trifluoroethyl)acrylamide (TFEAM) polymerization in water, providing fluorine-rich self-assembled nanoparticles in a single step. The resulting nanoparticles had different morphologies and sizes ranging from 60 to 220 nm. After optimizing their structure to maximize the magnetic relaxation of the fluorinated core, we obtained a strong 19F NMR/MRI signal in an aqueous environment. Their non-toxicity was confirmed on primary human dermal fibroblasts. Moreover, we visualized the nanoparticles by 19F MRI, both in vitro (in aqueous phantoms) and in vivo (after subcutaneous injection in mice), thus confirming their biomedical potential.

O.S. and V.M.P. acknowledge the financial support from Czech Grant Foundation (grant Nr. 22-03102S) and Charles University Prague (grant PRIMUS/21/SCI/007). D.H. acknowledges the financial support from the Czech Grant Foundation (project number 22-02836S). D.J. acknowledges the financial support from the Ministry of Health of the Czech Republic (NU22-08-00286) and from the project National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES, P r o j e c t no. LX22NPO5104)Funded by the European UnionNext Generation EU. The authors thank Dr. Carlos V. Melo for editing the manuscript.