Programming Self-Assembly and Stimuli-Triggered Response of Hydrophilic Telechelic Polymers with Sequence-Encoded Hydrophobic Initiators

A recent communication from our laboratory demonstrated that the presence of a small hydrophobic initiator residue (core) in water-soluble telechelic dibromo homopolymers can drive their self-assembly in aqueous solution into micelle-like nano-objects in which polymer chains adopt a folded conformation. Centered on the use of site-selective cleavable difunctional initiators, we demonstrate herein that this approach offers bottom-up and facile access to multistimuli-sensitive nanostructures for effective cargo delivery. Here, we first report the synthesis of homopolymers and copolymers encoding hydrophobicity and cleavable sites in their initiator residue in a precise sequence by single-electron transfer living radical polymerization (SET-LRP) from oligo­(ethylene glycol) (macro)­monomers. Employing a designed acid pH/UV light dual-cleavable initiator integrating a 2-nitroresorcinol diacetal sequence enabled on-demand middle-chain scission of the polymer chains and hence rapid/slow breakdown of the assemblies upon appropriate stimulation. Additionally, the possibility to interrogate binary co-delivery systems sequence-encoded with complimentary reactivity with combinatorial stimuli not only allows for fine-tuning the guest molecule release kinetics but also provides a mechanism to achieve control of their release behavior when different cargos are loaded.