Reactive Oxygen Species‐Responsive Selenium‐Containing Hybrid Polyester Based on the Polylactide‐Block‐Polycarbonate

ABSTRACT Hybrid polyesters synthesized by copolymerization of functionalized monomers exhibit integrated properties and expanded applications. Herein, we report a novel reactive oxygen species (ROS)‐responsive hybrid polyester composed of polylactic acid (PLA) and diselenide‐containing polycarbonate segments, derived from ring‐opening polymerization of the lactic acid‐derived O‐carboxyanhydride (LacOCA) and functionalized macrocyclic carbonate monomers. Interestingly, the copolymerization of the monomers proceeded via a two‐step strategy, affording well‐defined block copolymers. Specifically, the PLA segment should first be synthesized as a macroinitiator and subsequently employed to initiate the polymerization of the cyclic carbonate monomers. Theoretical calculations revealed significant reactivity differences among the monomers and the kinetically controlled mechanism of copolymerization, verifying the feasibility of the optimal synthetic route. 1 H NMR, 13 C NMR, and diffusion‐ordered spectroscopy collectively confirmed the successful synthesis and elucidated the chemical structure of the block hybrid polyester. The hybrid polyester exhibited enhanced thermal stability relative to pure PLA, and XRD showed a weaker crystalline peak with a distinct amorphous halo. Meanwhile, this copolymer displayed excellent ROS‐responsiveness attributed to the cleavage of diselenide bonds. Microspheres were then fabricated, and EDS mapping revealed the uniform distribution of selenium without aggregation. These microspheres displayed distinct ROS‐triggered degradation and release behaviors, indicating great potential in stimuli‐responsive delivery systems.