Water-dispersible monodispersed nanoparticles of magnetic γ-Fe2O3 and non-magnetic γ-Fe2O3@ZnO, γ-Fe2−2xZn2xO3 for targeting, imaging and therapy of cancer†

Abstract

We developed the monodispersed nanoparticles of magnetic γ-Fe₂O₃ and non-magnetic γ-Fe₂O₃@ZnO (CS), γ-Fe_2−2xZn_2xO₃ (SUB) systems for targeting, imaging and therapy of cancer. These nanoparticles are hydrophobic owing to the presence of oleic acid capping ligands on their surface and are coated with silica (@Si) and amine NH₂ groups to make them water-dispersible. These nanoparticles are further covalently conjugated with folic acid (FA) and fluorescein-5-isothiocyanate (FITC) and non-covalently loaded with the drug molecule doxorubicin hydrochloride (DOX). The following formulations were prepared: γ-Fe₂O₃@Si, γ-Fe₂O₃@Si-NH₂, γ-Fe₂O₃@Si-NH₂-FA, γ-Fe₂O₃@Si-NH₂-FA-FITC, γ-Fe₂O₃@Si-NH₂-FA-DOX, CS@Si, CS@Si-NH₂, CS@Si-NH₂-FA, CS@Si-NH₂-FA-FITC, CS@Si-NH₂-FA-DOX, SUB@Si, SUB@Si-NH₂, SUB@Si-NH₂-FA, SUB@Si-NH₂-FA-FITC and SUB@Si-NH₂-FA-DOX. The folic acid-coated γ-Fe₂O₃@Si-NH₂-FA, CS@Si-NH₂-FA and SUB@Si-NH₂-FA samples exhibit good bio-compatibility in normal cells (WI26, human lung fibroblast cell line). γ-Fe₂O₃@Si-NH₂-FA-FITC, CS@Si-NH₂-FA-FITC and SUB@Si-NH₂-FA-FITC nanoparticles show more cellular uptake and targeting toward MCF-7 (human breast cancer cell line) than toward A549 (human lung cancer cell line) cells, as confirmed through imaging. γ-Fe₂O₃@Si-NH₂-FA-DOX, CS@Si-NH₂-FA-DOX and SUB@Si-NH₂-FA-DOX show more toxicity toward MCF-7 cancer cells than toward A549 cancer cells. The IC₅₀ values for γ-Fe₂O₃@Si-NH₂-FA-DOX, CS@Si-NH₂-FA-DOX and SUB@Si-NH₂-FA-DOX were 4, 3.5 and 7.5 μM in MCF-7 and 6, 8 and 18 μM in A549, respectively. Drug release in an acidic microenvironment with a pH of 5 is greater than that at a pH of 7.4. The monodispersed nanoparticles developed in this study could be useful in drug delivery, targeting, imaging and therapy of cancer.