Thermo- and ROS-Responsive Self-Assembled Polymer Nanoparticle Tracers for 19F MRI Theranostics

Fluorine-19 magnetic resonance imaging (F-19 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 F-19 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-(feffocenylcarboxamido)ethyllacrylamide (FcCEA) monomer, which is hydrophobic and diamagnetic in the reduced electroneutral (Fe(II), ferrocene) state but hydrophilic and paramagnetic in the oxidized (Fe(III), feffocenium cation) state. This property can be useful for theranostic purposes (therapy and diagnostic purposes), especially, in terms of ROS-responsive drugdelivery 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.

Automated summary

In this study, polymer tracers for F-19 MRI were modified by introducing a redox-responsive monomer, allowing for changes in physicochemical properties in an oxidative environment. These ROS-responsive polymers have potential applications in theranostic purposes, especially in terms of drug delivery systems sensitive to oxidative environments in tumors or inflamed tissues.