BSA-Coated Copper Ferrite Nanoparticles Loaded with Doxorubicin for Synergistic Ferroptosis-Chemotherapy for Cancer Treatment.

Overcoming chemoresistance and systemic toxicity of chemotherapeutic molecules such as doxorubicin (DOX) remains a critical challenge in cancer treatment. Ferroptosis, an iron-dependent cell death mechanism driven by lipid peroxidation, presents a promising strategy to circumvent chemotherapeutic resistance. In this study, we reported a simple method for the preparation of uniform bovine serum albumin-coated copper ferrite nanoparticles (CuFe2O4@BSA) to deliver DOX. In the acidic environment, the CuFe2O4@BSA dissociated to release metal ions, which catalyzed Fenton reaction to produce hydroxyl radical (·OH) and induced ferroptosis. DOX could induce apoptosis and simultaneously enhance reactive oxygen species production, which further combined with ferroptosis, leading to the lipid peroxide and cell death. In vivo studies demonstrated that the nanoparticles achieved remarkable tumor suppression via this dual-action strategy, highlighting the great potential of integrating ferroptosis with conventional chemotherapy.