Anticancer Property of Iron Oxide Nanoparticle-Drug Complexes: An In Vitro Study.

Tumor-specific targeting of chemotherapeutic drugs can increase the therapeutic efficacy of most anticancer drugs. On surface-modified iron oxide nanoparticles (NPs), we complexed a hypoxic cell-targeting agent, sanazole (SAN), and a cytotoxic isoquinoline alkaloid, berberine (BBN). The major objective of this study was to elucidate the molecular mechanism of cytotoxicity in murine tumor cells (DLA) induced by NP-BBN-SAN complexes. The cytotoxicity of these complexes was determined using the dye exclusion method. The induction of apoptosis and cellular DNA damage in these cells was analyzed using dual staining and comet assay, respectively. The expression of genes in the treated cells elucidated the molecular mechanism underlying cytotoxicity. Cells treated with NP-BBN-SAN complexes showed significant increases in cytotoxicity and apoptosis, as well as extensive damage to cellular DNA compared to control cells. The cells treated with NP-BBN-SAN complexes showed greater DNA damage compared with other treatments. The increase in the expression of a pro-apoptotic gene suggested that apoptosis was the mechanism underlying cytotoxicity induced by NP-BBN-SAN complexes. Complexing with SAN increased the cytotoxic potential of NP-BBN complexes. Further in vivo studies are needed to evaluate the potential application of this method in controlling tumors.