Invertible vesicles and micelles formed by dually-responsive diblock random copolymers in aqueous solutions.

Dually responsive diblock random copolymers poly(nPA0.8-co-DEAEMA0.2)-block-poly(nPA0.8-co-EA0.2) were made from N-n-propylacrylamide (nPA), 2-(diethylamino)ethyl methacrylate (DEAEMA) and N-ethylacrylamide (EA) via reversible addition-fragmentation chain transfer (RAFT) polymerization. Copolymers of different block length ratios, poly(nPA28-co-DEAEMA7)-block-poly(nPA29-co-EA7) (P1) and poly(nPA28-co-DEAEMA7)-block-poly(nPA70-co-EA18) (P2), self-assemble into vesicles and micelles, responding to external stimuli in aqueous solutions, and both show "schizophrenic" inversion behavior when the pH and temperature are varied. The relative lengths of the two blocks are shown to affect the self-assembly of amphiphilic diblock copolymers. P1 has a similar length for both blocks and forms spherical vesicles with the first block poly(nPA29-co-EA7) as the membrane inner layer at pH 7 and 37 °C (above the cloud point of the more hydrophobic block, CP1), while spherical micelle-like aggregates are obtained at pH 10 and 25 °C (above CP1) with the second block poly(nPA28-co-DEAEMA7) as the core. In comparison, P2 has a different block length ratio (1 : 3, thus a much longer second block) and forms spherical micelles above CP1 at both pH 7 (the second block as the core) and pH 10 (the first block as the core). Further aggregation was observed by heating the polymer solution above the cloud point of the more hydrophilic block (CP2). The variation of the length and chemical composition of the blocks allows the tuning of the responsiveness of the block copolymers toward both pH and temperature and determines the formation of either micelles or vesicles during the aggregation.

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.