High Drug Capacity Doxorubicin-Loaded Iron Oxide Nanocomposites for Cancer Therapy

Abstract

Magnetic nanoparticles (MNPs) have great potential in the drug delivery area. Iron oxide (Fe3O4) MNPs have demonstrated a promising effect due to their ferrimagnetic properties, large surface area, stability, low cost, easy synthesis, and functionalization. Some coating procedures are required to improve stability, biocompatibility, and decrease toxicity for medical applications. Herein, the co-precipitation synthesis of iron oxide MNPs coated with four types of primary surfactants, polyethylene glycol 2000 (PEG 2000), oleic acid (OA), Tween 20 (Tw20), and Tween 80 (Tw80), were investigated. Dynamic light scattering (DLS), ζ-potential, and transmission electron microscopy (TEM) techniques were used for morphology, size, charge, and stability analysis. Methylene blue reactive oxygen species (ROS) detection assay and the toxicity experiment on the lung adenocarcinoma A549 cell line were conducted. Two loading conditions for anticancer drug doxorubicin (DOX) on MNPs were proposed. The first one provides high loading efficiency (~90%) with up to 870 μg/mg (DOX/MNPs) drug capacity. The second is perspective for extremely high capacity 1757 μg/mg with drug wasting (DOX loading efficiency ~24%). For the most perspective MNP_OA and MNP_OA_DOX in cell media, pH 7.4, 5, and 3, the stability experiments are also presented. MNP_OA_DOX shows DOX pH-dependent release in the acidic pH and effective inhibition of A549 cancer cell growth. The IC50 values were calculated as 1.13 ± 0.02 mM in terms of doxorubicin and 0.4 ± 0.03 µg/mL in terms of the amount of the nanoparticles. Considering this, the MNP_OA_DOX nano theranostics agent is a highly potential candidate for cancer treatment.

Keywords

• iron oxide nanoparticles
• functionalization
• coating
• polyethylene glycol
• oleic acid
• tween