Bimetallic organic cages as precise theranostic nanoplatforms for self-enhanced magnetic resonance imaging and chemodynamic therapy

Chemodynamic therapy (CDT) faces efficiency and safety challenges due to glutathione (GSH) overexpression in the tumor microenvironment (TME) and the lack of therapeutic feedback. In this study, a ferrocene (Fc) decorated metal organic cage (MOC-Fc) was constructed through coordination self-assembly between Fc-based ligands and copper ions, and its bimetallic synergistic and oxidation-responsive feature enables the theranostic integration of self-enhanced CDT and magnetic resonance imaging (MRI). The obtained MOC-Fc possesses an atomically precise cage-like structure with uniformly ultrasmall size. <i>In vitro</i> experiments demonstrated that MOC-Fc could effectively catalyze the Fenton-like reaction and significantly enhance the ROS-induced cell death through bimetal mediated GSH depletion. Concurrently, the MOC-Fc exhibited exceptionally <i>T</i>₁-weighted MRI capabilities due to the TME responsive states of the bimetal ions. In a nude mouse model of subcutaneous pancreatic cancer implantation, MOC-Fc successfully achieved MRI of the tumor and significantly inhibited its growth without significant systemic toxicity. This work proposes a novel paradigm for the development of precise, highly efficient, and visualized CDT nanoplatforms, and its catalytic-imaging bifunctional integration strategy establishes a theoretical foundation for the precision treatment of tumors and clinical translation.