Main-chain degradable, pH-responsive and covalently cross-linked nanoparticles via a one-step RAFT-based radical ring-opening terpolymerization

[Display omitted] •Straightforward procedure simultaneously incorporate main-chain ester bonds and multiple functionalities.•Post self-assembly covalent cross-linking is achieved without triggering undesirable degradability.•Reversible pH-induced swelling does not trigger undesirable degradability.•Nanoparticle degradation is achieved upon demand. Stimuli-responsive polymeric nanoparticles are very attractive materials often developed for the uptake and controlled release of active molecules, especially in personal and consumer care, agriculture and biomedical applications. However, a significant challenge for polymer scientists is the incorporation of specific functionality and stimuli-responsiveness, while simultaneously including a degradability mechanism to prevent undesirable build-up of the nanoparticle after its specific function is complete. We report, a straightforward synthetic strategy for the preparation of pH-responsive and covalently cross-linked polymeric nanoparticles possessing degradable ester-links in the main-chain of their linear polymer building blocks. This is achieved by combining reversible-addition fragmentation chain-transfer (RAFT) polymerization of conventional vinyl monomers with radical ring-opening polymerization of a cyclic ketene acetal monomer. A PEGylated macro-RAFT chain transfer agent facilitates the radical copolymerization of 2-(diethylamino)ethyl methacrylate, N-hydroxysuccinimide ester methacrylic acid and 2-methylene-1,3-dioxepane affording stimuli-responsive and activated ester functional copolymers which possess ester bonds periodically within their main-chain. These polymers undergo pH-triggered self-assembly. Subsequent, nanoparticle covalent cross-linked is achieved via amide bond formation, while maintaining a degradability mechanism through hydrolysis of the main-chain ester bonds.