Tuning the thermoresponsive properties of PEG-based fluorinated polymers and stimuli responsive drug release for switchable 19F magnetic resonance imaging

A series of terpolymers of styrene, oligoethylene glycol methyl ether methacrylate and 2,2,2-trifluoroethyl acrylate were synthesized by free radical polymerization. The lower critical solution temperature (LCST) of the polymers was tuned to close to physiological temperature by controlling the hydrophobic (styrene) content. The thermoresponsive properties of the polymers were studied by nuclear magnetic resonance spectroscopy, UV-vis spectroscopy and dynamic light scattering experiments. The effect of styrene content on 1H and 19F NMR, 19F T2 relaxation times and 19F magnetic resonance imaging (MRI) was examined in detail at various temperatures. It was observed that above the LCST the 19F MR imaging intensity drops, as a consequence of enhanced dipolar interactions involving 19F spins. These results aided the design of a thermo- and pH-responsive 19F MRI agent by incorporation of a hydrophobic model drug via an acid cleavable hydrazone linkage. It was demonstrated that with the release of the model hydrophobic drug, the LCST of the polymer was elevated due to reduced hydrophobicity, enhancing the 19F MRI signal at the given measurement temperature. The results provide the basis for the development of switchable 19F MR-guided theranostic platforms for targeted drug delivery of hydrophobic chemotherapeutic drugs as well as quantifying the amount of drug released at the target site.