pH-Responsive Micellar Nanoassemblies from Water-Soluble Telechelic Homopolymers Endcoding Acid-Labile Middle-Chain Groups in Their Hydrophobic Sequence-Defined Initiator Residue.

A middle-chain cleavable telechelic poly(oligoethylene glycol) methyl ether acrylate) (MCCT-POEGA-Br) was synthesized by single-electron transfer living radical polymerization (SET-LRP) initiated from an acetal-containing hydrophobic sequence-defined difunctional initiator. In aqueous medium, above a certain concentration, this hydrophilic homopolymer self-assembled into nanogel-like large micelles that exhibit an encapsulating capacity for both hydrophobic and hydrophilic cargo. The sequence-defined cleavage pattern encoded in the initiator residue allowed precise middle-chain cleavage, leading to quantitative disassembly of the corresponding nanoobjects. Dye release studies performed in an acidic environment demonstrated the potential of this new design concept in the preparation of pH-responsive nanocarriers. In addition, fluorescently tagged nanoassemblies could also be obtained via the thio-bromo "click" modification of MCCT-POEGA-Br prior to self-assembly. This strategy may provide facile access to a diversity of multistimuli-responsive nanocarriers based on commercially available hydrophilic monomers and sequence-defined difunctional initiators synthesized by this simple design strategy.