A water-dispersible Ori-loaded Fe-MOF NPs with suitable particle size and good biocompatibility were successfully synthesized and modified with tumor-targeting FA on its surface. The obtained Fe-MOF-FA@Ori NPs possess low cytotoxicity, good drug loading capacity, and pH-responsive drug release property. Meanwhile, the Fe-MOF-FA@Ori NPs exhibit better cancer therapeutic efficiency and could signally induce apoptosis, interfere with the cell cycle progression, and inhibit the migration ability of SMMC-7721 cells.

Oridonin (Ori) is a natural active component with superior anticancer properties; however, its clinical application is severely limited by the inherent properties of short half-life, limited bioavailability, and low water solubility. Some metal–organic frameworks (MOFs) materials have unique porous structure and appropriate nanometer particle size that are attractive in drug delivery. Herein, a folic acid (FA)-functionalized Fe-MOF was designed to efficiently incorporate Ori for targeting delivery to cancer cells and improve anticancer effects. The synthesized Fe-MOF-FA@Ori showed an average particle size of 200 nm with a loading capacity of 12.57%. The cytotoxicity assay confirmed that Fe-MOF-FA@Ori was effective in inhibiting the proliferation of SMMC-7721 cells. Mechanistically, the synthesized nanoparticle induced apoptosis and blocked the progression of the G0/G1 phase cell cycle on SMMC-7721 cells. Cell metastasis and invasion assays demonstrated that Fe-MOF-FA@Ori had good anti-metastatic ability against SMMC-7721 cells. Overall, Fe-MOF-FA is a potent drug carrier for targeting cancer therapy.