Bi2O3 gated Fe3O4@ZrO2 core/shell drug delivery system for chemo/ionic synergistic therapeutics

Abstract Magnetic mesoporous ZrO2 (Fe3O4@ZrO2, MMZr) nanoparticles blocked by bismuth oxide (Bi2O3) are presented and efficiently deliver chemotherapeutic agent daunomycin (DNM) to the targeted tumor cells. Bi2O3 not only rapidly dissolves in the acidic condition of cancer cells to release the loaded chemotherapeutic drug but also enhances the anti-cancer effect through synergistic effects of the chemotherapy and Bi3+ ions. By monitoring the treatment process, compared with the free drug DNM, the drug loaded DDS exhibit more significant suppression against cancerous cells growth such as A549 and MCF-7 cancer cells and lower cytotoxicity against normal Hacat cells. Mechanism research indicates that the drug loaded DDS can arrest the cell cycle at G0/G1 phase, change the mitochondrial membrane potential and finally induced the apoptosis of the cancerous cells. These results indicate that the Bi2O3-gated ZrO2 platform is a promising approach to serve as a pH-sensitive DDS in the treatment of various cancers by chemo/ionic synergistic effects.