Photodynamic Therapy (PDT) offers a promising minimally invasive treatment for breast cancer, but its efficacy is limited by the hostile tumor microenvironment (TME), including hypoxia and high glutathione (GSH) levels. Although various strategies to improve oxygen concentration or reduce reactive oxygen species (ROS) resistance for enhanced PDT have been explored, they typically require intricate design and complex synthesis of multifunctional nanocarriers. Thus, this study introduces a facile K2FeO4-induced strategy to enhance PDT efficiency in breast cancer through the tumor in situ synthesis of Fe2O3 and O2. Inspired by the successful application of K2FeO4 in ecological remediation and hemostasis, K2FeO4 reacts with GSH, biological system, H2O2, and water, to generate Fe2O3 and O2. Intratumoral injection of K2FeO4 improves the TME, followed by Ce6 administration to enhance PDT through synergistic ferroptosis. This approach boosts PDT efficacy significantly by increasing ROS generation, lipid peroxidation, and inhibiting GSH and GPX4. Proteomic analysis revealed alterations in key pathways, including endocytosis and energy metabolism. This K2FeO4-PDT strategy creates a positive feedback loop by enhancing oxidative stress, providing an interesting and promising approach to PDT.
Keywords: ferroptosis; iron oxide; photodynamic therapy; potassium ferrate (VI).
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