pH-Controlled Hierarchical Assembly/Disassembly of Multicompartment Micelles in Water

Multicompartment micelles (MCMs) have become attractive drug delivery systems as they allow the separate storage of two or more incompatible cargos in their core compartments (e.g., drugs and dyes for imaging). A recent hierarchical self-assembly process for hydrophobic terpolymers in organic solvents showed the ability to form very homogeneous MCM populations, yet the transfer of this process into water requires a better understanding of the formation mechanism and influence of chain mobility during assembly. Here, the synthesis of a linear poly(oligo(ethylene glycol) methacrylate)-block-poly(benzyl acrylate)-block-poly(4-vinylpyridine) (POEGMA-b-PBzA-b-P4VP) triblock terpolymer by reversible addition-fragmentation chain transfer (RAFT) polymerization is reported as well as its step-wise assembly into MCMs in water with POEGMA corona, PBzA patches, and P4VP core. Reversible assembly/disassembly of the MCMs is investigated through protonation/deprotonation of the P4VP core. Interestingly, the low glass transition temperature (T_g ) of the hydrophobic PBzA middle block causes MCMs to directly disassemble into molecularly dissolved chains instead of patchy micelles due to mechanical stress from electrosteric repulsion of the protonated P4VP corona chains. In addition, pH resistant MCMs are created by core-crosslinking and fluorescent properties are added by covalent anchoring of fluorescent dyes via straightforward click chemistry.