Uptake of dimercaptosuccinate-coated magnetic iron oxide nanoparticles by cultured brain astrocytes

Magnetic iron oxide nanoparticles (Fe-NP) are currently considered for various diagnostic and therapeutic applications in the brain. However, little is known on the accumulation and biocompatibility of such particles in brain cells. We have synthesized and characterized dimercaptosuccinic acid (DMSA...

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Veröffentlicht in:Nanotechnology 2011-04, Vol.22 (14), p.145101
Hauptverfasser: Geppert, Mark, Hohnholt, Michaela C, Thiel, Karsten, Nürnberger, Sylvia, Grunwald, Ingo, Rezwan, Kurosch, Dringen, Ralf
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container_end_page
container_issue 14
container_start_page 145101
container_title Nanotechnology
container_volume 22
creator Geppert, Mark
Hohnholt, Michaela C
Thiel, Karsten
Nürnberger, Sylvia
Grunwald, Ingo
Rezwan, Kurosch
Dringen, Ralf
description Magnetic iron oxide nanoparticles (Fe-NP) are currently considered for various diagnostic and therapeutic applications in the brain. However, little is known on the accumulation and biocompatibility of such particles in brain cells. We have synthesized and characterized dimercaptosuccinic acid (DMSA) coated Fe-NP and have investigated their uptake by cultured brain astrocytes. DMSA-coated Fe-NP that were dispersed in physiological medium had an average hydrodynamic diameter of about 60 nm. Incubation of cultured astrocytes with these Fe-NP caused a time- and concentration-dependent accumulation of cellular iron, but did not 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 at 4 °C was drastically lowered compared to cells that had been incubated at 37 °C. Electron microscopy revealed the presence of Fe-NP-containing vesicles in cells that were incubated with Fe-NP at 37 °C, but not in cells exposed to the nanoparticles at 4 °C. These data demonstrate that cultured astrocytes efficiently take up DMSA-coated Fe-NP in a process that appears to be saturable and strongly depends on the incubation temperature.
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However, little is known on the accumulation and biocompatibility of such particles in brain cells. We have synthesized and characterized dimercaptosuccinic acid (DMSA) coated Fe-NP and have investigated their uptake by cultured brain astrocytes. DMSA-coated Fe-NP that were dispersed in physiological medium had an average hydrodynamic diameter of about 60 nm. Incubation of cultured astrocytes with these Fe-NP caused a time- and concentration-dependent accumulation of cellular iron, but did not 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 at 4 °C was drastically lowered compared to cells that had been incubated at 37 °C. Electron microscopy revealed the presence of Fe-NP-containing vesicles in cells that were incubated with Fe-NP at 37 °C, but not in cells exposed to the nanoparticles at 4 °C. 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Electron microscopy revealed the presence of Fe-NP-containing vesicles in cells that were incubated with Fe-NP at 37 °C, but not in cells exposed to the nanoparticles at 4 °C. 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subjects Animals
Animals, Newborn
Astrocytes - cytology
Astrocytes - metabolism
Astrocytes - ultrastructure
Brain - cytology
Cell Membrane - metabolism
Cell Membrane - ultrastructure
Cell Survival
Cells, Cultured
Cytoplasmic Vesicles - metabolism
Cytoplasmic Vesicles - ultrastructure
Endocytosis
Intracellular Space - metabolism
Iron - metabolism
Kinetics
Light
Magnetite Nanoparticles - chemistry
Magnetite Nanoparticles - ultrastructure
Microscopy, Electron, Transmission
Particle Size
Rats
Rats, Wistar
Scattering, Radiation
Spectrometry, X-Ray Emission
Static Electricity
Succimer - chemistry
Succimer - metabolism
Temperature
title Uptake of dimercaptosuccinate-coated magnetic iron oxide nanoparticles by cultured brain astrocytes
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