Polyelectrolyte coated gadolinium doped cobalt ferrite nanoparticles for cancer therapy

Abstract

In the current study, polyglutamic acid grafted chitosan coated (PGA/CH) and gadolinium (Gd) doped CoFe2O4 nanoparticles with the formula of PGA/CH@CoFe2-xGdxO4 (x = 0.0, 0.1, 0.3 and 0.5) were synthesized and intended to be utilized both as a magnetic hyperthermia and drug delivery agent. First, CH@CoFe2-xGdxO4 nanoparticles were synthesized by in situ co-precipitation method and then PGA was grafted onto chitosan coated magnetic nanoparticles. The spinel phase formation without an impurity phase (for x ≤ 0.3) was confirmed via x-ray diffractometry. Scanning electron microscope energy dispersive spectroscopy results verify that Gd3+-doping percentage of ≈5 and ≈ 15% were achieved into cobalt ferrite without any impurity phase. Dynamic light scattering analysis showed that nanoparticles with CH functionalization, the CH@CoGd0.5Fe1.5O4 nanoparticle showed remarkable decrease in hydrodynamic sizes (from 743 ± 19 to 162 ± 25 nm), which indicates that CH coating prevent the nanoparticles from aggregation. The low amount (6 wt%) of bare CoFe2O4 nanoparticles dispersed in viscous glycerol provided a temperature increase of 6.6 °C/min when exposed to alternating magnetic field of 1048 kHz frequency and 5.8 kA/m amplitude. The temperature and pH dependent Doxorubicin (DOX) drug release profiles of the PGA/CH@CoGd0.5Fe1.5O4 nanoparticles were investigated at 37 and 42 °C and by using three different pH buffer solutions (PBS 4.5, 6.5 and 7.4). Grafting an anionic PGA onto cationic CH ensured the selective burst release at pH:6.5 (pH of tumor microenvironment is ∼6.7) at 42 °C. MTT assay and the colony formation assay results showed that PGA/CH@CoGd0.1Fe1.9O4 nanoparticles without DOX, do not exhibit significant toxicity against MDA-MB-231 and HEK-293 cells.