Polymeric 19F MRI agents responsive to reactive oxygen species

Abstract

Medical imaging agents that can report on the biological state are attracting increasing interest. Here we report the development of novel ¹⁹F polymeric imaging agents that are activated by reactive oxygen species (ROS). The imaging agents composed of thioether- and fluorine-containing methacrylate monomers were synthesised using atom transfer radical polymerisation (ATRP) from a hydrophilic poly(ethylene glycol)-based initiator. In aqueous solution, the agents self-assemble into nanoparticles with compact hydrophobic cores. The mobility of the fluorinated segments within the cores is greatly restricted, thereby significantly shortening the ¹⁹F T₂ relaxation times and attenuating the ¹⁹F NMR signal. However, upon treatment with ROS (i.e. H₂O₂), the hydrophobic thioether groups of the agents are oxidised to hydrophilic sulfoxide groups, resulting in the disassembly of the aggregated nanoparticles. The disassembly of the ¹⁹F MRI agents lengthens the T₂ relaxation times, and enables an appreciable enhancement of ¹⁹F NMR signal. ¹⁹F MRI of solutions of the polymers before and after oxidation demonstrated a remarkable “OFF–ON” regulation in response to ROS. The sensitivity of the imaging agents was further enhanced by adding a pH switch, resulting in a ROS/pH dual-responsive ¹⁹F MRI agent. The most pronounced change in intensity of the ¹⁹F NMR/MRI signal was achieved in response to the presence of ROS in a mildly acidic environment. The work demonstrates that these novel polymeric ¹⁹F MRI agents hold great potential for improved diagnosis and therapy of diseases presenting high levels of ROS.