Easy access to 19F-labeled nanoparticles for use as MRI contrast probes via self-assembly of fluorinated copolymers synthesized by sequential RAFT polymerization

•We report a novel approach for preparing 19F-labeled nanoparticles in only two-steps (polymer synthesis and self-assembly).•The sequential RAFT polymerization technique allowed control over the distribution of fluorine atoms in the copolymer.•Well-defined sub-100 nm spherical particles in water were obtained.•19F NMR revealed a narrow Lorentzian peak for copolymers featuring a specific distribution of fluorine atoms.

The one-pot, sequential RAFT polymerization technique was applied to the synthesis of partially fluorinated quasi-block copolymers consisting of 2,2,2-trifluoroethyl (meth)acrylate (TFE(M)A) and oligo(ethylene glycol)methyl ether (meth)acrylate (OEG9(M)A) repeating units. Starting with the polymerization of a methacrylate monomer followed by an acrylate, two sets of samples, differing mainly in terms of the distribution of hydrophobic and hydrophilic domains, were prepared, namely: POEG9MA-b-P(OEG9MA-co-TFEA)-C12 (1a–e) and PTFEMA-b-P(TFEMA-co-OEG9A)-C12 (2a–e). Whilst the polymers of both series lead to sub-100 nm spherical particles upon self-assembly in water, 19F NMR experiments revealed that the microenvironments where fluorine atoms are located in the colloids are different. Multiple 19F NMR peaks with low signal-to-noise ratios and large half-widths were evidenced for the nanoparticles 1a–e. In contrast, a narrow Lorentzian peak (half-width avg. = 160 Hz) with a spin-lattice relaxation time (T1) typical of micellar systems (T1 avg. = 365 ms) verified the good potential of the systems 2a–e as 19F MRI probes when the molar fraction of the fluorinated monomer is ca. 35%. This clear structure-property relationship correlates with the complex self-assembly behavior of fluorinated amphiphilic polymers.

Graphical abstract19F-labeled nanoparticles ready for use as MRI contrast probes were prepared in only two main steps involving one-pot RAFT polymerization and self-assembly from ethanol. Sub-100 nm spherical particles were characterized by a narrow Lorentzian peak in the 19F NMR spectrum when ca. 35 mol% of fluorinated monomer is present.Figure optionsDownload full-size imageDownload as PowerPoint slide