Thermoresponsive behaviour of poly[(oligo(ethyleneglycol methacrylate)]s and their protein conjugates: importance of concentration and solvent system

Thermoresponsive poly[oligo(ethyleneglycol) methacrylate]s with a variety of different oligo(ethyleneglycol) graft lengths were synthesised by reversible-addition fragmentation chain transfer (RAFT) polymerisation. The lower critical solution temperature (LCST) behaviour of these polymers was evaluated as a function of the polymer concentration and the concentration of dissolved solutes, in order to understand their applicability for in vitro and in vivo applications. It was observed that in the relevant dilute (<1 mg mL−1) concentration range the observed LCSTs increased by approximately 6 °C compared to higher concentrations. This was confirmed by complimentary dynamic light scattering and differential scanning calorimetry measurements. The impact of biological solutions on the LCST was determined using bovine blood plasma, which resulted in observed LCSTs lower than what is found in traditional buffer or pure aqueous solutions. Finally, a well-defined polymer–protein conjugate was synthesised by ‘grafting from’ using single-electron transfer (SET) polymerisation. This model polymer–protein therapeutic also displayed similar concentration dependant behaviour, highlighting the importance of testing novel ‘smart’ materials and conjugates at both relevant concentration ranges and in appropriate solvent systems in order to use them in biotechnological applications.