Towards nanoparticles with site-specific degradability by ring-opening copolymerization induced self-assembly in organic medium

Reversible addition–fragmentation chain transfer (RAFT)-mediated radical ring-opening copolymerization-induced self-assembly (rROPISA) in heptane at 15 wt% solids was successfully applied to the copolymerization of benzyl methacrylate (BzMA) with 2-methylene-1,3-dioxepane (MDO) from a poly(lauryl methacrylate) (PLMA) macro-RAFT agent. Despite less efficient control of the copolymerization compared to similar copolymerizations with 2-methylene-4-phenyl-1,3-dioxolane (MPDL) or 5,6-benzo-2-methylene-1,3-dioxepane (BMDO), it yielded stable, diblock copolymer nanospheres (D_z = 100–200 nm) containing tunable amounts of polycaprolactone (PCL)-like degradable units in the core (F_MDO = 0.04–0.19), resulting in significant degradation under accelerated hydrolytic conditions. Synthesis of surface-degradable diblock copolymer nanoparticles was then performed through the synthesis of P(LMA-co-BMDO) and P(LMA-co-MPDL) macro-chain transfer agents (CTAs). Even though partial livingness during chain extension with BzMA by PISA was noticed, stable nanospheres were obtained for F_BMDO = 0.05 and porous nanospheres for F_BMDO = 0.08–0.09, whose average diameters increased with the BMDO content. Attempts to prepare “all-degradable” vinyl particles were also made by rROPISA of BzMA and BMDO (or MPDL) from degradable macro-CTAs showing degradation in agreement with the copolymers’ expected structure.