EDTA capped iron oxide nanoparticles magnetic micelles: drug delivery vehicle for treatment of chronic myeloid leukemia and T1–T2 dual contrast agent for magnetic resonance imaging

Abstract

Ethylene diamine tetra acetate (EDTA) capped Fe₃O₄ nanoparticles (NPs) have been synthesized and encapsulated using polymeric micelles. The synthesized Fe₃O₄/EDTA/P magnetic micelles are used as a vehicle to load the hydrophobic drug imatinib and transfect it in a bone marrow cell-line (K562) in vitro for the treatment of chronic myeloid leukemia. From FTIR spectroscopy it is established that EDTA coordinates bidentately with the surface Fe ions. From the vibrating sample magnetometry (VSM) study, the shape of the magnetization curve indicates superparamagnetic behavior in the presence of a magnetic field. The hydrodynamic diameter measured by dynamic light scattering (DLS) is found to be 440 nm within the upper limit (500 nm) required to transfect into the cell. An in vitro drug release kinetics study reveals that approximately 60% of the drug is released at the end of 196 h. Notably, the drug-loaded magnetic micelles display much lower liver accumulation compared to the bare drug, indicating prolonged circulation time and maximum availability at the bone marrow. In vivo magnetic resonance (MR) imaging conducted on nude mice bearing the synthesized magnetic micelle after i.v. administration reveals excellent imaging capabilities, in dual mode, especially 24 h post-injection. We propose that the longitudinal relaxation (T₁) of water protons can be induced by mimicking Gd-DTPA chelate chemistry while transverse relaxation (T₂) can be achieved by controlling the particle size.