Engineering CeO₂/CuO heterostructure anchored on upconversion nanoparticles with boosting ROS generation-primed apoptosis-ferroptosis for cancer dynamic therapy

Highly toxic reactive oxygen species (ROS) induced apoptosis and ferroptosis have been considered as significant cell death pathways for cancer therapy. However, insufficient amount of intracellular ROS extremely restricts the therapeutic effect. Toward this, we report a rationally designed nanocomposite (mUCC) with enhanced ROS generation ability, inducing the combination of apoptosis and ferroptosis through synergistic photodynamic therapy (PDT) and chemodynamic therapy (CDT). Under 808 nm near-infrared (NIR) light irradiation, photocatalytic reaction is triggered starting from the separation of electron–hole pairs on the surface of heterojunction (CeO₂/CuO), realizing improved ROS production. Simultaneously, mUCC served as Fenton-like agent exhibits considerable ability to generate highly toxic ·OH under tumor microenvironment (TME). The boosted accumulation of ROS disrupts the redox balance within tumor cells and results in the integration of apoptosis and ferroptosis. In addition, mUCC shows satisfactory tumor targeting property benefiting from the cancer cell membrane functionalization under the guidance of magnetic resonance imaging (MRI) and NIR fluorescence imaging. The intelligent mUCC with good biocompatibility and excellent antitumor response achieves efficient tumor elimination under synergistic PDT and CDT. This work offers an elective approach for further development of ROS-based therapeutic nanoplatform in cancer therapy.