EDTA capped iron oxide nanoparticles magnetic micelles: drug delivery vehicle for treatment of chronic myeloid leukemia and T-1-T-2 dual contrast agent for magnetic resonance imaging

摘要

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 ( T-1) of water protons can be induced by mimicking Gd-DTPA chelate chemistry while transverse relaxation ( T-2) can be achieved by controlling the particle size.