Degradable Cationic Polyesters with Tunable Anion-Induced Upper Critical Solution Temperature Coacervation

High Resolution Image Download MS PowerPoint Slide Herein, we report degradable cationic polyesters combining pH responsiveness with tunable, anion-induced UCST phase behavior in aqueous media under mildly acidic and physiologically relevant pH conditions, accompanied by reversible self-coacervation. These main-chain polyesters feature ionizable amine side groups paired with Cl – (PE-Cys-Cl) or BF 4 – (PE-Cys-BF 4 ) counterions, enabling UCST transitions triggered by NaCl, NaBF 4, and notably by the pharmaceutically relevant anion salicylate (SAL). Cloud point temperature was tuned over a broad range of 8–91 °C by controlling anion type, pH, polymer concentration, and the anion-to-cation repeat unit ratio (A/CRU). Mechanistic studies revealed liquid–liquid phase separation into dynamic, water-rich coacervate droplets. Importantly, the hydrolytic degradation was strongly counterion-dependent, with PE-Cys-Cl exhibiting substantial degradation under physiological conditions compared to low-molecular-weight PLLA, whereas the more hydrophobic PE-Cys-BF 4 polymer remained largely unchanged. These materials provide a versatile proof-of-concept platform for anion-triggered UCST phase separation, opening opportunities in responsive coacervation, anion sensing, and drug delivery related applications.