Ce(III)/Ce(IV) Oxide Nanohybrids in Zwitterionic Polybetaine-Based Polyion Complexes for Tunable Redox Catalysis

Abstract Cerium oxide nanoparticles (nanoceria, CeOx) have attracted broad interest as inorganic nanozymes owing to their intrinsic redox enzyme-mimicking activity arising from reversible Ce3+/Ce4+ valence cycling; however, their practical utility remains limited by poor colloidal stability in protein-rich biological environments. To address this challenge, zwitterionic double-hydrophilic block copolymers, poly(sulfobetaine methacrylate)-block-poly(methacrylic acid) (P(SBMA)-b-P(MAA)), were synthesized via reversible addition−fragmentation chain transfer polymerization and employed for the aqueous-phase fabrication of cerium-based hybrid polyion complex nanoparticles (HPICs). Stoichiometric coordination of Ce3+ ions to the P(MAA) block induced self-assembly into core-corona nanoparticles comprising a Ce3+-rich polyion complex core encapsulated by a zwitterionic P(SBMA) corona (Ce-HPICs). A notable consequence of Ce3+ coordination was the emergence of upper critical solution temperature-type thermoresponsive behavior in the P(SBMA) coronaabsent in the uncomplexed copolymerreversibly switchable by electrolyte modulation. Controlled oxidation under mild alkaline conditions afforded a second platform, CeOx-HPICs, bearing mixed-valence Ce3+/Ce4+ oxide domains with a chemically tunable Ce3+/Ce4+ ratio (0.23 to 1.63), as confirmed by X-ray photoelectron spectroscopy. The two platforms exhibited complementary nanozyme behaviors: Ce-HPICs demonstrated superior peroxidase-like activity owing to radical-generating Ce3+ sites, while CeOx-HPICs exhibited enhanced peroxide decomposition kinetics attributable to defect-rich ceria-like domains. Crucially, both platforms maintained excellent colloidal stability and antifouling performance in human serum albumin solution, in stark contrast to free Ce3+ ions and bare ceria nanoparticles, which underwent pronounced aggregation under identical conditions. These results establish the P(SBMA)-b-P(MAA)-mediated HPIC platform as a versatile strategy for constructing colloidal nanozymes with chemically tunable redox activity and superior stability in protein-rich biological environments.