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. A pH‐responsive polymer‐CeO2 hybrid with an optimized hydrodynamic diameter creates nanoreactors to boost their oxidative activity in acidic environments by confining the oxygen and/or biological substrates inside the hybrid and promoting the charge transfer between the catalysts and substrates and enables pH‐dependently selective tumor catalytical chemodynamic therapy.