Stimuli-Responsive Thiomorpholine Oxide-Derived Polymers with Tailored Hydrophilicity and Hemocompatible Properties

Thermo-responsive hydrophilic polymers, including those showing tuneable lower critical solution temperature (LCST), represent a continuous subject of exploration for a variety of applications, but particularly in nanomedicine. Since biological pH changes can inform the organism about the presence of disequilibrium or diseases, the development of dual LCST/pH-responsive hydrophilic polymers with biological potential is an attractive subject in polymer science. Here, we present a novel polymer featuring LCST/pH double responsiveness. The monomer ethylthiomorpholine oxide methacrylate (THOXMA) can be polymerised via the RAFT process to obtain well-defined polymers. Copolymers with hydroxyethyl methacrylate (HEMA) were prepared, which allowed the tuning of the LCST behaviour of the polymers. Both, the LCST behaviour and pH responsiveness of hydrophilic PTHOXMA were tested by following the evolution of particle size by dynamic light scattering (DLS). In weak and strong alkaline conditions, cloud points ranged between 40-60 degrees C, while in acidic medium no LCST was found due to the protonation of the amine of the THOX moieties. Additional cytotoxicity assays confirmed a high biocompatibility of PTHOXMA and haemolysis and aggregation assays proved that the thiomorpholine oxide-derived polymers did not cause aggregation or lysis of red blood cells. These preliminary results bode well for the use of PTHOXMA as smart material in biological applications.