Monacolin-K loaded MIL-100(Fe) metal-organic framework induces ferroptosis on metastatic triple-negative breast cancer

Breast cancer is the most common disease among women worldwide. Triple-negative breast cancer (TNBC) is the most aggressive and has the worst prognosis. MIL-100(Fe) is a promising metal-organic framework (MOF). MIL100(Fe) was loaded with monacolin K (MK) to form MK@MIL-100(Fe). MK was a natural compound with anticancer properties. The surface of MK@MIL-100(Fe) was coated with iron oxide (Fe3O4), 3 O 4 ), and the microwave hydrothermal method was used to form the material MK@MIL-100(Fe)/Fe3O4 3 O 4 with metal-organic properties, which effectively increases the accumulation of reactive oxygen species and lipids in cancer cells. In the mouse model of metastatic TNBC formed by tail vein injection of 4 T1 cells, MK@MIL-100(Fe)/Fe3O4 3 O 4 inhibited the occurrence of metastatic TNBC without hair shedding, and no side effects were found. In cell and mouse experiments, expressions of ferroptosis-related proteins, glutathione peroxidase (GPX4), and 3-hydroxy-3-methylglutaryl-coA reductase (HMGCR) were reduced. Apoptotic regulatory factors were increased, as BH3 interacting- domain death agonist (BID), apoptosis-inducing factor (AIF), endonuclease G (Endo-G), bcl2-associated X protein (BAX) and caspase-3 (Casp3). Therefore, we demonstrated that the MOF has been functionalized to enhance its biocompatibility and iron targeting ability, and MK@MIL-100(Fe)/Fe3O4 3 O 4 served as a nanomedicine to inhibit TNBC through ferroptosis and apoptosis.