Fluorinated Ferrocene Moieties as a Platform for Redox-Responsive Polymer F-19 MRI Theranostics

Fluorine-19 magnetic resonance imaging (F-19 MRI) stands out as a powerful tool for noninvasive diagnostics. In particular, polymer-based F-19 MRI tracers offer tunable physicochemical properties, including solubility and thermoresponsiveness, and enhanced F-19 MRI performance. However, these tracers do not detectably respond to redox changes or do so in only one redox state, thereby preventing potential applications to reactive oxygen species (ROS) bioimaging. Herein, we report the first amphiphilic redox-responsive, poly(2-oxazoline)-based polymers bearing fluorinated ferrocene moieties. Their hydrophobicity and redox responsiveness were tailored by changing the monomer ratio and substitution pattern of the fluorinated ferrocene units. Converting the diamagnetic fluorinated ferrocene moieties into paramagnetic ferrocenium markedly changed the chemical shift and relaxation times of the F-19 nuclei distinguishable by F-19 MRI. In turn, the statistical-diblock copolymers formed nanoparticles that disassemble upon oxidation, with no toxicity to cultured cells. Therefore, these polymers may be used to release lipophilic drugs in ROS-rich malignancies.