Switchable Vesicles Formed by Diblock Random Copolymers with Tunable pH- and Thermo-Responsiveness

The thermo-responsiveness of polymers in aqueous media can be tuned by the choice of comonomers used in the synthesis of block copolymers made of random sequences of the same comonomers but of different molar ratios. The same synthetic approach may be applied to other stimuli and we have made diblock random copolymers with both pH- and thermo-responsiveness and studied the formation of vesicles whose membrane core and coronas may be inverted in aqueous media. Sequential reversible addition–fragmentation chain transfer (RAFT) polymerization was used to prepare well-defined block copolymers in the form of AₙBₘ-b-AₚCq, where A, B, and C are N-n-propylacrylamide (nPA), 2-(diethylamino)ethyl methacrylate (DEAEMA), and N-ethylacrylamide (EA), respectively. This polymer shows interesting “schizophrenic” behavior in aqueous solutions. Both blocks are thermo-responsive, and one block is pH-responsive in which the tertiary amine group of DEAEMA may be protonated at a lower pH. A molecularly dissolved polymer is obtained at neutral pH and ambient temperature. At pH 7 and 37 °C, the polymer self-assembles into vesicles with the poly(nPA₀.₈-co-EA₀.₂) block as the membrane core (mean hydrodynamic diameter of the vesicles Dₕ = 148 nm). In an alkaline medium (pH 10) at 25 °C, the membrane core and the coronas of the vesicles are inverted with poly(nPA₀.₈-co-DEAEMA₀.₂) block forming the core (Dₕ = 60 nm). In addition, two-step phase transitions are observed in both alkaline and neutral solutions corresponding to the cloud points of the individual blocks. Here, the random nature of the blocks allows fine-tuning the thermo-responsiveness based solely on lower critical solution temperatures and its combination with pH-sensitivity provides vesicles with switchable membrane core and corona in aqueous solution.