Fabrication of etoposide-loaded folic-acid-clocked mesoporous nanoparticles: Investigation of lung cancer proliferation and induction of apoptosis and ferroptosis

Abstract

Etoposide (EPT) offers significant benefits in the tumor therapy domain. EPT may cause ferroptosis in lung cancer cells; however, its limited bioavailability and low water solubility inhibit its potential applications. Therefore, we investigated the properties of EPT-loaded folic acid clocked with mesoporous silica nanoparticles (MSNs) (FA-MSN@EPT) that target lung tumor cells. We assessed the capacities of MSN@EPT and FA-MSN@EPT to induce ferroptosis in lung cancer cells by measuring ferroptosis-related ferritin (Fe2+), malondialdehyde, and glutathione levels. Enhanced ferroptosis, inhibition of A549 and H1299 cell proliferation, migration, invasion, and considerable improvements in the EPT bioavailability were noted when the fabricated MSN@EPT and FA-MSN@EPT were utilized. Furthermore, the apoptotic mode of cell death was investigated by acridine orange and ethidium bromide (AO-EB) and 4′,6-diamidino-2-phenylindole (DAPI) staining and flow cytometry using annexin V-FITC and propidium iodide staining. This opens new possibilities for the clinical treatment of various tumors and offers a possible therapeutic option for lung cancer.