Abstract
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). MIL-100(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), and the microwave hydrothermal method was used to form the material MK@MIL-100(Fe)/Fe3O4 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 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-methyl-glutaryl-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 served as a nanomedicine to inhibit TNBC through ferroptosis and apoptosis.
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