An Iron Oxide Nanoparticle Drug Carrier for Improved Cancer Chemotherapy in Drug Resistance Line

We have previously reported the aqueous phase synthesis of mono-dispersive Fe₃O₄ nanoparticles with amine group surface modification. The nanoparticles exhibit satisfactory biocompatibility and significant MRI contrast in both in vitro and in vivo models. The magnetite nanoparticles could be manipulated by externally applied magnetic field. In this study, we have modified the naoparticle as an anti-cancer chemotherapeutic agent that capable of magnetic field guided targeting while traceable by MRI. We evaluate the anti-cancer drug epirubicin loading capacity and efficiency by spectrophotometric measurement. The epirubicin loaded onto the nanoparticles was proportional to the added substrate and a typical loading efficiency is close to 100 % at lower concentration that reached a plateau at 0.2% initial drug concentration for 2 muM of nanoparticle in 1mL reaction volume. We than evaluated the anticancer efficacy of the epirubicin loaded nanoparticle complex using a drug resistant cell line MBT-2. An improved cytotoxicity of to the cancer cell line was revealed by WST-1 assay for the drug loaded nanoparticle compared to free drugs of the same dosage. A dosage dependent cancer cell cytotoxicty was noticed in the test dosage range for the drug loaded on the nanoparticles but not in the free drug groups. In conclusion, the current study demonstrated a magnetite nanoparticle served as an alternative anti-cancer drug carrier. In addition to its magnetic force manipulation and MRI contrast property, the magnetite carrier was able to overcome drug resistance of cancer cells and obtained an improved in vitro chemotherapeutic efficacy. Future works to explore the possible molecular and cellular mechanisms behind its anti-drug resistance as well as in vivo animal model validation is warranted.