A metal–organic framework Ce-BDA for triple-modal cancer therapy: chemodynamic therapy, chemotherapy and immunotherapy

A cerium-based metal-organic framework, Ce-BDA, was selected and further loaded with manganese ions (Mn²⁺) and chemotherapeutic drug doxorubicin (DOX) to construct a multifunctional system, denoted as Mn&DOX@Ce-BDA. Taking advantage of the valence-switching capability of Ce³⁺/Ce⁴⁺, Mn&DOX@Ce-BDA can efficiently trigger reactive oxygen species (ROS) production <i>via</i> a Fenton-like reaction in weakly acidic tumor microenvironment. Notably, the released Mn²⁺ serves a dual function as it acts as a co-catalyst to amplify ROS generation for enhanced chemodynamic therapy (CDT) while also activating dendritic cells to secrete pro-inflammatory cytokines and interferons, thereby exerting potent immunotherapeutic effects. Furthermore, this nanoplatform enables the tumor-specific controlled release of DOX, facilitating the synergy of chemotherapy. By integrating chemodynamic therapy, chemotherapy, and immunotherapy into a single nanosystem, Mn&DOX@Ce-BDA achieves highly efficient and selective tumor cell killing, providing a promising triple-combination therapeutic strategy to overcome the limitations of conventional cancer treatments.