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Fluorine-19 magnetic resonance imaging (19F MRI) enables detailed in vivo tracking of fluorine-containing tracers and is therefore becoming a particularly useful tool in noninvasive medical imaging. In previous studies, we introduced biocompatible polymers based on the hydrophilic monomer N-(2-hydroxypropyl)methacrylamide (HPMA) and the thermoresponsive monomer N-(2,2-difluoroethyl)acrylamide (DFEA). These polymers have abundant magnetically equivalent fluorine atoms and advantageous properties as 19F MRI tracers. Furthermore, in this pilot study, we modified these polymers by introducing a redox-responsive monomer. As a result, our polymers changed their physicochemical properties once exposed to an oxidative environment. Reactive oxygen species (ROS)-responsive polymers were prepared by incorporating small amounts (0.9-4.5 mol %) of the N-[2-(ferrocenylcarboxamido)ethyl]acrylamide (FcCEA) monomer, which is hydrophobic and diamagnetic in the reduced electroneutral (Fe(II), ferrocene) state but hydrophilic and paramagnetic in the oxidized (Fe(III), ferrocenium cation) state. This property can be useful for theranostic purposes (therapy and diagnostic purposes), especially, in terms of ROS-responsive drug-delivery systems. In the reduced state, these nanoparticles remain self-assembled with the encapsulated drug but release the drug upon oxidation in ROS-rich tumors or inflamed tissues.

Magnetic resonance imaging (MRI) using 19F-based tracers has emerged as a promising multi-purpose noninvasive diagnostic tool and its application requires the use of various 19F-based tracers for the intended diagnostic purpose. In this study, we report a series of double-stimuli-responsive polymers for use as injectable implants, which were designed to form implants under physiological conditions, and to subsequently dissolve with different dissolution rates (t1/2 ranges from 30 to more than 250 days). Our polymers contain a high concentration of fluorine atoms, providing remarkable signal detectability, and both a hydrophilic monomer and a pH-responsive monomer that alter the biodistribution properties of the implant. The implant location and dissolution were observed using 19F MRI, which allows the anatomic extent of the implant to be monitored. The dissolution kinetics and biocompatibility of these materials were thoroughly analyzed. No sign of toxicity in vitro or in vivo or pathology in vivo was observed, even in chronic administration. The clinical applicability of our polymers was further confirmed via imaging of a rat model by employing an instrument currently used in human medicine.

The poly(2-methyl-2-oxazoline)-b-poly[N-(2,2-difluoroethyl)acrylamide] self-assembled nanoparticles show great potential in biological applications as, e.g., 19F MRI tumour diagnostic agents. As such their internal structure needs to be thoroughly investigated while the results also help to understand temperature-dependent self-assembly behaviour of copolymers comprised of the hydrophilic and thermoresponsive blocks in general. In this paper, we elucidate internal structure of the nanoparticles formed by temperature-driven self-assembly of the abovementioned diblock copolymer by various methods. The majority of our polymers form micelle-like structures above the cloud point temperature (CPT). However, the presence of thermoresponsive homopolymer chains even in amounts below standard detection limits as well as strong hydrogen bonding causes the formation of larger aggregates interconnected by hydrophobic networks and hydrogen bonds, which contain large amounts of solvent. In the case of our particles, we also observe a strong influence of solvent on CPT, particle formation and overall sample behaviour. The ability of nanoparticles to provide usable 19F NMR signal was also confirmed.