Versatile Platform to Degradable Bottlebrush Polymers via Cascade Metathesis Polymerization of Enyne Macromolecules with Polyacetal Backbones

Abstract Bottlebrush polymers have attracted increasing attention owing to their unique molecular architecture and broad potential in biomedical and functional material applications. Graft-through ring-opening metathesis polymerization has emerged as an efficient method for constructing well-defined bottlebrush polymers. However, the typically nondegradable backbones of the resultant polymers limit their suitability in application scenarios where controlled clearance and degradability are required. Herein, we report a modular synthetic approach to the construction of degradable bottlebrush polymers with a polyacetal backbone based on cascade enyne metathesis polymerization. Biomass-derived enyne monomers were used as a unified modular platform to construct a diverse macromonomer library with switchable side chain compositions through multiple living polymerization techniques, including RAFT, ATRP, anionic ROP, and cationic ROP. The macromonomer library generally exhibited controlled grafting-through polymerization behavior, enabling predictable molecular weight control and relatively narrow molecular weight distributions. Importantly, the degradation kinetics of the polyacetal backbone can be effectively modulated by controlling the acetal regiochemistry at the monomer level. Furthermore, degradable amphiphilic bottlebrush block copolymers were synthesized and self-assembled into uniform micelles with tunable morphological size and low critical micelle concentrations as well as degradability under acidic conditions mimicking the tumor microenvironment. This work provides a versatile platform for the design of structurally precise and degradable bottlebrush polymers with tunable properties and advances their potential as drug delivery carriers.