Mark Geppert

Publications of Mark Geppert

• Magnetic field-induced acceleration of the accumulation of magnetic iron oxide nanoparticles by cultured brain astrocytes.

  Authors: Marie-Christin Lamkowsky, Mark Geppert, Maike M Schmidt, Ralf Dringen

  Journal of biomedical materials research. Part A. 11/2011;

  Magnetic iron oxide nanoparticles (Fe-NPs) are considered for various biomedical and neurobiological applications that involve the presence of external magnetic fields. However, little is known onMagnetic iron oxide nanoparticles (Fe-NPs) are considered for various biomedical and neurobiological applications that involve the presence of external magnetic fields. However, little is known on the effects of a magnetic field on the uptake of such particles by brain cells. Cultured brain astrocytes accumulated dimercaptosuccinate-coated Fe-NP in a time-, temperature-, and concentration-dependent manner. This accumulation was strongly enhanced by the presence of the magnetic field generated by a permanent neodymium iron boron magnet that had been positioned below the cells. The magnetic field-induced acceleration of the accumulation of Fe-NP increased almost proportional to the strength of the magnetic field applied, increasing the cellular-specific iron content from an initial 10 nmol/mg protein within 4 h of incubation at 37°C to up to 12,000 nmol/mg protein. However, presence of a magnetic field also increased the amounts of iron that attached to the cells during incubation with Fe-NP at 4°C. These results suggest that the presence of an external magnetic field promotes in cultured astrocytes both the binding of Fe-NP to the cell membrane and the internalization of Fe-NP. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.

• Treatment with iron oxide nanoparticles induces ferritin synthesis but not oxidative stress in oligodendroglial cells.

  Authors: Michaela C Hohnholt, Mark Geppert, Ralf Dringen

  Acta biomaterialia. 07/2011; 7(11):3946-54.

  Magnetic iron oxide nanoparticles (IONPs) have been used for a variety of neurobiological applications, although little is yet known as to the fate of such particles in brain cells. To address theseMagnetic iron oxide nanoparticles (IONPs) have been used for a variety of neurobiological applications, although little is yet known as to the fate of such particles in brain cells. To address these questions, we have exposed oligodendroglial OLN-93 cells to dimercaptosuccinate-coated IONPs. Treatment of the cells strongly increased the specific cellular iron content proportional to the IONP concentrations applied (0-1000 μM total iron as IONPs) up to 300-fold, but did not cause any acute cytotoxicity or induce oxidative stress. To investigate the potential of OLN-93 cells to liberate iron from the accumulated IONPs, we have studied the upregulation of the iron storage protein ferritin and the cell proliferation as cellular processes that depend on the availability of low-molecular-weight iron. The presence of IONPs caused a concentration-dependent increase in the amount of cellular ferritin and partially bypassed the inhibition of cell proliferation by the iron chelator deferoxamine. These data demonstrate that viable OLN-93 cells efficiently take up IONPs and suggest that these cells are able to use iron liberated from accumulated IONPs for their metabolism.

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

  Authors: Mark Geppert, Michaela C Hohnholt, Karsten Thiel, Sylvia Nürnberger, Ingo Grunwald, Kurosch Rezwan, Ralf Dringen

  Nanotechnology. 02/2011; 22(14):145101.

  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 biocompatibilityMagnetic 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.

• Magnetic field-induced acceleration of the accumulation of magnetic iron oxide nanoparticles by cultured brain astrocytes.

  Authors: Marie-Christin Lamkowsky, Mark Geppert, Maike M. Schmidt und Ralf Dringen

  Biomedical Material Research: Part A. 01/2011;

• Effects of iron chelators, iron salts, and iron oxide nanoparticles on the proliferation and the iron content of oligodendroglial OLN-93 cells.

  Authors: Michaela Hohnholt, Mark Geppert, Ralf Dringen

  Neurochemical research. 05/2010; 35(8):1259-68.

  The oligodendroglial cell line OLN-93 was used as model system to investigate the consequences of iron deprivation or iron excess on cell proliferation. Presence of ferric or ferrous iron chelatorsThe oligodendroglial cell line OLN-93 was used as model system to investigate the consequences of iron deprivation or iron excess on cell proliferation. Presence of ferric or ferrous iron chelators inhibited the proliferation of OLN-93 cells in a time and concentration dependent manner, while the application of a molar excess of ferric ammonium citrate (FAC) prevented the inhibition of proliferation by the chelator deferoxamine. Proliferation of OLN-93 cells was not affected by incubation with 300 microM iron that was applied in the form of FAC, FeCl(2), ferrous ammonium sulfate or iron oxide nanoparticles, although the cells efficiently accumulated iron during exposure to each of these iron sources. The highest specific iron content was observed for cells that were exposed to the nanoparticles. These data demonstrate that the proliferation of OLN-93 cells depends strongly on the availability of iron and that these cells efficiently accumulate iron from various extracellular iron sources.

• Accumulation of citrate-coated magentic iron oxide nanoparticles by cultured brain astrocytes

  Authors: Michaela C Hohnholt, Mark Geppert, Sylvia Nürnberger, Janek von Byern, Ingo Grunwald, Ralf Dringen

  Advanced Engineering Materials. 01/2010; 12:B690-B694.

• Accumulation of iron oxide nanoparticles by cultured brain astrocytes.

  Authors: Mark Geppert, Michaela Hohnholt, Linda Gaetjen, Ingo Grunwald, Marcus Bäumer, Ralf Dringen

  Journal of biomedical nanotechnology. 06/2009; 5(3):285-93.

  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 forMagnetic 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.