Accumulation of Iron Oxide Nanoparticles by Cultured Brain Astrocytes

Abstract

Magnetic iron oxide nanoparticles are considered for various diagnostic and therapeutic applications in brain including their use as contrast agent for magnetic resonance imaging or as tool for magnetic drug delivery. However, little is known so far on the consequences of a treatment of brain cells with such nanoparticles. In order to study the biocompatibility of iron oxide nanoparticles and the accumulation of iron from such particles in brain cells, we have used astrocyte-rich primary cultures as model system. Iron oxide nanoparticles were chemically synthesized with a yield of about 80% regarding the iron content. Transmission electron microscopy revealed that the synthesized iron oxide nanoparticles had a diameter of about 10 nm. Exposure of astrocyte cultures to 100 microM iron that were supplied as citrate-coated iron oxide nanoparticles did not cause any acute loss in cell viability but resulted in an almost linear increase in the cellular iron content that reached after 6 h of incubation at 37 degrees C a total cellular iron content of about 300 nmol/mg protein. The rate of iron accumulation from iron oxide nanoparticles was significantly higher than that from the low molecular weight iron complex ferric ammonium citrate (FAC). Lowering the incubation temperature from 37 degrees C to 4 degrees C reduced the iron accumulation rate from iron oxide nanoparticles or FAC by about 60%. In addition, presence of ferric or ferrous iron chelators did not affect the cellular iron accumulation from iron oxide nanoparticles. These data suggest that cultured astrocytes are able to accumulate intact iron oxide nanoparticles.