Chemodynamic therapy (CDT) is defined as the generation of abundant ROS inside tumor tissue by a Fenton reaction-based nanocatalyst, which is characterized by high selectivity and few side effects. However, the rate of ROS generation by Fenton reaction is limited due to a scarcity of Fenton-based catalysts within cells and a high level of intracellular antioxidant agents. In this study, a heterogeneous Fenton nanocatalyst, copper ferrite nanoparticles (CuFe2O4), was synthesized and it was accompanied by oxaliplatin (Oxa), a ROS-producing chemotherapeutic drug. CuFe2O4 was synthesized through the hydrothermal method and bovine serum albumin was used as a biological capping agent. The nanoparticles possessed a high surface area and mesoporous structure with an extremely small particle size of about 6.1 nm. Nanoparticles had a high capacity for oxaliplatin (3.4 mg g−1) and were then modified in situ by polydopamine (PDA) via alkaline-triggered polymerization, resulting in a pH-sensitive drug delivery system. The final construct (CuFe2O4.Oxa@PDA) showed pH-responsive drug release in a time-staggered manner. In vitro studies disclosed that CuFe2O4.Oxa@PDA nanoparticles were internalized by breast cancer cells (4T1), inhibiting tumor cell growth more effectively than free oxaliplatin. Furthermore, less cytotoxicity was observed against normal cells (NIH3T3), indicating that the construct's cytotoxic effects are directed solely at tumor cells. Furthermore, CuFe2O4.Oxa@PDA effectively catalyzed the Fenton reaction inside tumor cells, allowing it to amplify intracellular oxidative stress by lowering intracellular GSH levels and inhibiting catalase activity. Based on these findings, CuFe2O4.Oxa@PDA could be used as an adjuvant nanoparticle along with oxaliplatin-based cancer chemotherapy, significantly reinforcing intratumoral oxidative stress and promoting the clinical efficacy of oxaliplatin.

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