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

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 BF₄^- (PE-Cys-BF₄) counterions, enabling UCST transitions triggered by NaCl, NaBF₄, 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-BF₄ 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.