Oxygen self-supplying small size magnetic nanoenzymes for synergistic photodynamic and catalytic therapy of breast cancer

Abstract

In recent years, tumor catalytic therapy based on nanozymes has attracted widespread attention. However, its application is limited by the tumor hypoxic microenvironment (TME). In this study, we developed oxygen-supplying magnetic bead nanozymes that integrate hemoglobin and encapsulate the photosensitizer curcumin, demonstrating reactive oxygen species (ROS)-induced synergistic breast cancer therapy. Fe₃O₄ magnetic bead-mediated catalytic dynamic therapy (CDT) generates hydroxyl radicals (˙OH) through the Fenton reaction in the tumor microenvironment. The Hb-encapsulated Fe₃O₄ magnetic beads can be co-loaded with the photosensitizer/chemotherapeutic agent curcumin (cur), resulting in Fe₃O₄-Hb@cur. Under hypoxic conditions, oxygen molecules are released from Fe₃O₄-Hb@cur to overcome the TME hypoxia, resulting in comprehensive effects favoring anti-tumor responses. Upon near-infrared (NIR) irradiation, Fe₃O₄-Hb@cur activates the surrounding molecular oxygen to generate a certain amount of singlet oxygen ⁽¹O₂), which is utilized for photodynamic therapy (PDT) in cancer treatment. Meanwhile, we validated that the O₂ carried by Hb significantly enhances the intracellular ROS level, intensifying the catalytic therapy mediated by Fe₃O₄ magnetic beads and inflicting lethal damage to cancer cells, effectively inhibiting tumor growth. Therefore, significant in vivo synergistic therapeutic effects can be achieved through catalytic–photodynamic combination therapy.