A pH-Responsive Polymer-CeO₂ Hybrid to Catalytically Generate Oxidative Stress for Tumor Therapy

Catalytic generation of reactive oxygen species has been developed as a promising methodology for tumor therapy. Direct O₂^•− production from intratumor oxygen exhibits exceptional tumor therapeutic efficacy. Herein, this therapy strategy is demonstrated by a pH-responsive hybrid of porous CeO₂ nanorods and sodium polystyrene sulfonate that delivers high oxidative activity for O₂^•− generation within acidic tumor microenvironments for chemodynamic therapy and only limited oxidative activity in neutral media to limit damage to healthy organs. The hydrated polymer–nanorod hybrids with large hydrodynamic diameters form nanoreactors that locally trap oxygen and biological substrates inside and improve the charge transfer between the catalysts and substrates in the tumor microenvironment, leading to enhanced catalytic O₂^•− production and consequent oxidation. Together with successful in vitro and in vivo experiments, these data show that the use of hybrids provides a compelling opportunity for the delivery selective chemodynamic tumor therapy.