Fluorinated Water-Soluble Poly(2-oxazoline)s as Highly Sensitive ¹⁹F MRI Contrast Agents

Abstract

Recently, 19F magnetic resonance imaging (MRI) emerged as a powerful noninvasive diagnostic tool in modern medicine. Fluorinated polymer materials represent an attractive class of MRI contrast agents (CAs) due to their structural variability and tunable properties. Herein, we describe for the first time the 19F MRI of CAs based on fluorinated water-soluble poly­(2-oxazoline)­s (PAOx), a polymer class with increasing popularity in biomedical sciences. A series of fluorinated PAOx with increasing fluorine content were synthesized by controlled side-chain hydrolysis of poly­(2-methyl-2-oxazoline) followed by reacylation of its ethylenimine units by difluoroacetic anhydride. As the increasing fluorine content leads to the copolymer hydrophobization, their composition was optimized for maximal 19F MRI performance while retaining good solubility in water. The magnetic properties of the water-soluble polymers were studied in vitro by 19F NMR and MRI, revealing their outstanding relaxation properties and imaging sensitivity. All CAs were found to be noncytotoxic for HeLa cells in vitro. Finally, the diagnostic potential of the new CAs was demonstrated by a successful in vivo 19F MRI visualization of the selected fluorinated polymer in rats.

Fluorine-Containing Block and Gradient Copoly(2-oxazoline)s Based on 2-(3,3,3-Trifluoropropyl)-2-oxazoline: A Quest for the Optimal Self-Assembled Structure for 19F Imaging

“…38 Water-soluble partially fluorinated poly(2methyl-2-oxazoline) copolymers were recently reported as MRI CAs. 39 Thermoresponsive CAs based on the fluorinecontaining comb-shaped poly-(2-oxazoline)s were described by Zhang et al 40 By varying the length of the side chain at the 2-oxazoline unit, the authors achieved bilateral changes in the MRI intensity. In 2013, Lee et al described the synthesis of partly fluorinated polyacrylamides, which demonstrate temperature-responsive behavior.…”

Poly(2‐oxazoline)‐ and Poly(2‐oxazine)‐Based Self‐Assemblies, Polyplexes, and Drug Nanoformulations—An Update

“…Yet another approach to introduce fluorinated moiety into POx chain was very recently presented by Sedlacek et al. [ 147 ] The fluorinated copolymers were prepared by partial hydrolysis and subsequent reacetylation using difluoroacetic anhydride, yielding (p(MeOx‐ co ‐2‐difluoromethyl‐2‐oxazoline) stat (p(MeOx‐ co ‐DFMeOx) stat ) The obtained copolymers were soluble in water at the concentration 50 g L −1 up to 34 mol% of fluorinated monomer. The copolymers did not exhibit self‐assembly behavior, as studied by DLS.…”

Iron-doped calcium phytate nanoparticles as a bio-responsive contrast agent in 1H/31P magnetic resonance imaging

“…A number of contrast agents have been proposed, notably non-toxic probes that are responsive to various biochemical stimuli, tissue-specific targeting and theranostics 2 – 4 . One of the most effective methods is non-hydrogen X-nuclei MR imaging, which provides complementary information to anatomical 1 H-MR imaging and visualisation of physiological processes 5 – 7 , even on a cellular level 8 . Phosphorus is one of the more promising X-nuclei and the second most commonly used nucleus in biological MR studies.…”