Uptake of dimercaptosuccinate-coated magnetic iron oxide nanoparticles by cultured brainastrocytes

Abstract

Magnetic iron oxide nanoparticles (Fe-NP) are currently considered for variousdiagnostic and therapeutic applications in the brain. However, little is known onthe accumulation and biocompatibility of such particles in brain cells. We havesynthesized and characterized dimercaptosuccinic acid (DMSA) coated Fe-NPand have investigated their uptake by cultured brain astrocytes. DMSA-coatedFe-NP that were dispersed in physiological medium had an average hydrodynamicdiameter of about 60 nm. Incubation of cultured astrocytes with these Fe-NPcaused a time- and concentration-dependent accumulation of cellular iron, but didnot lead within 6 h to any cell toxicity. After 4 h of incubation with 100–4000 µM iron supplied as Fe-NP, the cellular iron content reached levels between 200 and 2000 nmol mg − 1 protein. The cellular iron content after exposure of astrocytes to Fe-NP at4 °C was drastically lowered compared to cells that had been incubated at37 °C. Electronmicroscopy revealed the presence of Fe-NP-containing vesicles in cells that were incubated with Fe-NPat 37 °C, but not in cells exposed to the nanoparticles at4 °C. These data demonstrate that cultured astrocytes efficiently take up DMSA-coated Fe-NPin a process that appears to be saturable and strongly depends on the incubationtemperature.