Fluorinated Ferrocene Moieties as a Platform for Redox-Responsive Polymer <sup>19</sup>F MRI Theranostics
Pavel Švec, Oleg V. Petrov, Jan Lang, Petr Štěpnička, Ondřej Groborz, David J. Dunlop, Jan Blahut, Kristýna Kolouchová, Lenka Loukotová, Ondřej Sedláček, Tomáš Heizer, Zdeněk Tošner, Miroslav Šlouf, Hynek Beneš, Richard Hoogenboom, Martin Hrubý
Abstract
Fluorine-19 magnetic resonance imaging (19F MRI) stands out as a powerful tool for noninvasive diagnostics. In particular, polymer-based 19F MRI tracers offer tunable physicochemical properties, including solubility and thermoresponsiveness, and enhanced 19F 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 19F nuclei distinguishable by 19F 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.