Quantification of the aggregation of magnetic nanoparticles with different polymeric coatings in cell culture medium

Eberbeck, Dietmar; Kettering, Melanie; Bergemann, Ch.; Zirpel, P; Hilger, Ingrid; Trahms, Lutz

doi:10.1088/0022-3727/43/40/405002

Cited by 51 publications

(39 citation statements)

References 31 publications

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“…Additionally, interactions between NP coatings and extracellular proteins such as FBS might result in NP protein coronas that modify their hydrodynamic size and surface properties and therefore influence their cellular uptake. 12,68 Resovist ® and MCP are sterically stabilized with the sugar polymers carboxydextran and carboxymethyldextran, respectively, and thus are very similar to each other. The additional carboxymethyl groups in carboxymethyldextran account for the difference in surface charge (zeta potential) of MCP (−38.8 mV) and Resovist ® (−25.1 mV).…”

Section: Discussionmentioning

confidence: 99%

Labeling of mesenchymal stem cells for MRI with single-cell sensitivity

Schellenberger¹,

Kratz²,

Farr³

et al. 2016

IJN

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Sensitive cell detection by magnetic resonance imaging (MRI) is an important tool for the development of cell therapies. However, clinically approved contrast agents that allow single-cell detection are currently not available. Therefore, we compared very small iron oxide nanoparticles (VSOP) and new multicore carboxymethyl dextran-coated iron oxide nanoparticles (multicore particles, MCP) designed by our department for magnetic particle imaging (MPI) with discontinued Resovist ® regarding their suitability for detection of single mesenchymal stem cells (MSC) by MRI. We achieved an average intracellular nanoparticle (NP) load of >10 pg Fe per cell without the use of transfection agents. NP loading did not lead to significantly different results in proliferation, colony formation, and multilineage in vitro differentiation assays in comparison to controls. MRI allowed single-cell detection using VSOP, MCP, and Resovist ® in conjunction with high-resolution T2*-weighted imaging at 7 T with postprocessing of phase images in agarose cell phantoms and in vivo after delivery of 2,000 NP-labeled MSC into mouse brains via the left carotid artery. With optimized labeling conditions, a detection rate of ~45% was achieved; however, the experiments were limited by nonhomogeneous NP loading of the MSC population. Attempts should be made to achieve better cell separation for homogeneous NP loading and to thus improve NP-uptake-dependent biocompatibility studies and cell detection by MRI and future MPI. Additionally, using a 7 T MR imager equipped with a cryocoil resulted in approximately two times higher detection. In conclusion, we established labeling conditions for new high-relaxivity MCP, VSOP, and Resovist ® for improved MRI of MSC with single-cell sensitivity.

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Section: Discussionmentioning

confidence: 99%

Labeling of mesenchymal stem cells for MRI with single-cell sensitivity

Schellenberger¹,

Kratz²,

Farr³

et al. 2016

IJN

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“…This feature allows the discrimination of particles bound to specific biological entities [12] from particles embedded in body fluids, thus forming the basis for SPION imaging by MRX. The property was used, e.g., to image the accumulation of intravenously injected SPIONs in the spleen and liver of a mouse by MRX [13], or to quantify the aggregation of magnetic nanoparticles in cell cultures [14]. Many of the earlier studies used multi-core particles, while more recently larger single-core magnetic particles have shown large magnetic signals in observation windows ranging from 50 ms to 2 s [15].…”

Section: Introductionmentioning

confidence: 99%

A quantitative study of particle size effects in the magnetorelaxometry of magnetic nanoparticles using atomic magnetometry

Dolgovskiy

Lebedev

Colombo

et al. 2015

Journal of Magnetism and Magnetic Materials

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The discrimination of immobilised superparamagnetic iron oxide nanoparticles (SPIONs) against SPIONs in fluid environments via their magnetic relaxation behaviour is a powerful tool for bio-medical imaging.Here we demonstrate that a gradiometer of laser-pumped atomic magnetometers can be used to record accurate time series of the relaxing magnetic field produced by pre-polarised SPIONs. We have investigated dry in vitro maghemite nanoparticle samples with different size distributions (average radii ranging from 14 to 21 nm) and analysed their relaxation using the Néel-Brown formalism. Fitting our model function to the magnetorelaxation (MRX) data allows us to extract the anisotropy constant K and the saturation magnetisation M S of each sample. While the latter was found not to depend on the particle size, we observe that K is inversely proportional to the (time-and size-) averaged volume of the magnetised particle fraction. We have identified the range of SPION sizes that are best suited for MRX detection considering our specific experimental conditions and sample preparation technique.

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“…These effects are associated with absorbtion of serum proteins to the nanoparticle surface. 47 In connection with cellular uptake the same nanoparticle formulations were shown to be internalized in endolysosomes. We were also able to show, for the first time, that mitomycin C affects mRNA as well as the membrane MRP 1 and 3 protein expression.…”

Section: Discussionmentioning

confidence: 53%

The exposure of cancer cells to hyperthermia, iron oxide nanoparticles, and mitomycin C influences membrane multidrug resistance protein expression levels

Franke¹,

Kettering²,

Lange³

et al. 2013

IJN

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Purpose:The presence of multidrug resistance-associated protein (MRP) in cancer cells is known to be responsible for many therapeutic failures in current oncological treatments. Here, we show that the combination of different effectors like hyperthermia, iron oxide nanoparticles, and chemotherapeutics influences expression of MRP 1 and 3 in an adenocarcinoma cell line. Methods: BT-474 cells were treated with magnetic nanoparticles (MNP; 1.5 to 150 µg Fe/cm 2 ) or mitomycin C (up to 1.5 µg/cm 2 , 24 hours) in the presence or absence of hyperthermia (43°C, 15 to 120 minutes). Moreover, cells were also sequentially exposed to these effectors (MNP, hyperthermia, and mitomycin C). After cell harvesting, mRNA was extracted and analyzed via reverse transcription polymerase chain reaction. Additionally, membrane protein was isolated and analyzed via sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. Results: When cells were exposed to the effectors alone or to combinations thereof, no effects on MRP 1 and 3 mRNA expression were observed. In contrast, membrane protein expression was influenced in a selective manner. The effects on MRP 3 expression were less pronounced compared with MRP 1. Treatment with mitomycin C decreased MRP expression at high concentrations and hyperthermia intensified these effects. In contrast, the presence of MNP only increased MRP 1 and 3 expression, and hyperthermia reversed these effects. When combining hyperthermia, magnetic nanoparticles, and mitomycin C, no further suppression of MRP expression was observed in comparison with the respective dual treatment modalities. Discussion: The different MRP 1 and 3 expression levels are not associated with de novo mRNA expression, but rather with an altered translocation of MRP 1 and 3 to the cell membrane as a result of reactive oxygen species production, and with shifting of intracellular MRP storage pools, changes in membrane fluidity, etc, at the protein level. Our results could be used to develop new treatment strategies by repressing mechanisms that actively export drugs from the target cell, thereby improving the therapeutic outcome in oncology.

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Quantification of the aggregation of magnetic nanoparticles with different polymeric coatings in cell culture medium

Cited by 51 publications

References 31 publications

Labeling of mesenchymal stem cells for MRI with single-cell sensitivity

Labeling of mesenchymal stem cells for MRI with single-cell sensitivity

A quantitative study of particle size effects in the magnetorelaxometry of magnetic nanoparticles using atomic magnetometry

The exposure of cancer cells to hyperthermia, iron oxide nanoparticles, and mitomycin C influences membrane multidrug resistance protein expression levels

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