Supramolecular flower micelle formation of polyrotaxane-containing triblock copolymers prepared from macro-chain transfer agents bearing molecular hooks

Polyrotaxane (PRX)-containing triblock copolymers are a unique class of supramolecular polymers. In combination with the intrinsic properties of polymer chains, the supramolecular properties of PRXs, such as the freely mobile character of threading α-cyclodextrins (α-CDs) and the intermolecular hydrogen bonding, can be utilized as biomaterials. However, it is difficult to synthesize well-defined PRX-containing triblock copolymers with regulated polymeric chain length and the number of threading α-CDs. Herein, we described the precise synthetic method of PRX-containing triblock copolymers via reversible addition–fragmentation chain transfer (RAFT) polymerization using a novel PRX macro-chain transfer agent (CTA) with terminal hooks of phenylalanyl groups. The terminal phenylalanyl groups of PRX macro-CTA act as a hook to inhibit the dethreading of α-CDs during polymerization to achieve the regulation of molecular weight of the polymer chains while maintaining the number of threading α-CDs in the PRX segments. Additionally, we first prepared self-assembled polymeric micelles with an outermost PRX layer using the PRX-containing triblock copolymers. The hydroxyethyl group-modified triblock copolymers composed of PRX and hydrophobic poly(benzyl methacrylate) (PBzMA) were found to form polymeric micelles 47 nm in diameter and with a narrow size distribution. The supramolecular polymeric micelles show a core–shell-type structure comprising a core of hydrophobic PBzMA surrounded by the PRX flower loops. This micelle formation allows the incorporation of water-insoluble anticancer drugs within the PBzMA core as well as biological ligands into the α-CDs of the PRX flowers toward receptor proteins of target cell membranes. Finally, it is expected that the obtained polymeric micelles with the outermost PRX layer could be applied as a supramolecular drug carrier.