A Calcium-Overloading MOF Platform with Cuproptosis for Cancer Therapy and Inhibition of Cancer Cell Growth and Migration

The metal-organic framework Ca-BDC was synthesized from biocompatible Ca ions and terephthalic acid (H2BDC, 1,4-benzenedicarboxylic acid) and co-loaded with Cu ions and doxorubicin hydrochloride (DOX) to construct a multifunctional system Cu&DOX@Ca-BDC. It could produce reactive oxygen species (ROS) to realize chemodynamic therapy. Moreover, the system displayed stimulus-responsive drug release behaviors to realize chemotherapy. Within a cancer microenvironment, the system could induce mitochondrial dysfunction through intracellular calcium overload, ultimately triggering cancer cell death. Moreover, the system utilized Cu ion-mediated Fenton-like reactions to generate ROS and induced cuproptosis, which synergized with chemotherapy to achieve ideal anticancer effects. In addition, the material exhibited antibacterial activity against both E. coli and S. aureus, which could inhibit cancer cell migration effectively. The multimodal platform Cu&DOX@Ca-BDC provided a strategy for cancer combination therapy.