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Development and characterization of magnetic iron oxide nanoparticles with a cisplatin-bearing polymer coating for targeted drug delivery.

Unterweger H, Tietze R, Janko C, Zaloga J, Lyer S, Dürr S, Taccardi N, Goudouri OM, Hoppe A, Eberbeck D, Schubert DW, Boccaccini AR, Alexiou C - Int J Nanomedicine (2014)

Bottom Line: In this project, SPIONs with a dextran and cisplatin-bearing hyaluronic acid coating were successfully synthesized as a novel cisplatin drug delivery system.The resulting amide bond linkage was verified using Fourier transform infrared spectroscopy.In conclusion, combination of dextran-coated SPIONs with hyaluronic acid and cisplatin represents a promising approach for magnetic drug targeting in the treatment of cancer.

View Article: PubMed Central - PubMed

Affiliation: ENT Department, Section of Experimental Oncology and Nanomedicine (SEON), Else Kroener-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Germany.

ABSTRACT
A highly selective and efficient cancer therapy can be achieved using magnetically directed superparamagnetic iron oxide nanoparticles (SPIONs) bearing a sufficient amount of the therapeutic agent. In this project, SPIONs with a dextran and cisplatin-bearing hyaluronic acid coating were successfully synthesized as a novel cisplatin drug delivery system. Transmission electron microscopy images as well as X-ray diffraction analysis showed that the individual magnetite particles were around 4.5 nm in size and monocrystalline. The small crystallite sizes led to the superparamagnetic behavior of the particles, which was exemplified in their magnetization curves, acquired using superconducting quantum interference device measurements. Hyaluronic acid was bound to the initially dextran-coated SPIONs by esterification. The resulting amide bond linkage was verified using Fourier transform infrared spectroscopy. The additional polymer layer increased the vehicle size from 22 nm to 56 nm, with a hyaluronic acid to dextran to magnetite weight ratio of 51:29:20. A maximum payload of 330 μg cisplatin/mL nanoparticle suspension was achieved, thus the particle size was further increased to around 77 nm with a zeta potential of -45 mV. No signs of particle precipitation were observed over a period of at least 8 weeks. Analysis of drug-release kinetics using the dialysis tube method revealed that these were driven by inverse ligand substitution and diffusion through the polymer shell as well as enzymatic degradation of hyaluronic acid. The biological activity of the particles was investigated in a nonadherent Jurkat cell line using flow cytometry. Further, cell viability and proliferation was examined in an adherent PC-3 cell line using xCELLigence analysis. Both tests demonstrated that particles without cisplatin were biocompatible with these cells, whereas particles with the drug induced apoptosis in a dose-dependent manner, with secondary necrosis after prolonged incubation. In conclusion, combination of dextran-coated SPIONs with hyaluronic acid and cisplatin represents a promising approach for magnetic drug targeting in the treatment of cancer.

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Magnetization curves for different SEONDEX after normalization to the volume fraction of the magnetic phase.Note: All data sets showed no hysteresis and no remanence.Abbreviations: SEONDEX, dextran-coated SPIONs; SPIONs, superparamagnetic iron oxide nanoparticles.
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f5-ijn-9-3659: Magnetization curves for different SEONDEX after normalization to the volume fraction of the magnetic phase.Note: All data sets showed no hysteresis and no remanence.Abbreviations: SEONDEX, dextran-coated SPIONs; SPIONs, superparamagnetic iron oxide nanoparticles.

Mentions: The magnetic properties of SEONDEX are also very important because after administration of the drug delivery vehicles into the body, they are positioned in the tumor tissue with the aid of an external magnetic field. The magnetization curves for SEONDEX were recorded by means of SQUID measurements, which are depicted in Figure 5. All samples show superparamagnetic behavior, with a saturation magnetization dependent on the dextran concentration during precipitation (Table 3). The sample with the amount of lowest dextran showed a saturation magnetization of 454±23 kA/m, whereas the sample with the highest content showed a value of 186±10 kA/m. The value for SEONDEX 2.0 is comparable with that of bulk magnetite, the saturation magnetization of which is 480 kA/m at room temperature.46 In general, the decrease can be explained with the results outlined above. The X-ray diffraction patterns show lesser crystallinity with increasing dextran content, which is why the saturation magnetization is reduced. The curves also showed no hysteresis or residual magnetization. This is very important because once the applied field is removed from the particles, the lack of residual magnetization reduces the probability of agglomeration, thereby avoiding uptake by phagocytes as well as the danger of thrombosis.12


Development and characterization of magnetic iron oxide nanoparticles with a cisplatin-bearing polymer coating for targeted drug delivery.

Unterweger H, Tietze R, Janko C, Zaloga J, Lyer S, Dürr S, Taccardi N, Goudouri OM, Hoppe A, Eberbeck D, Schubert DW, Boccaccini AR, Alexiou C - Int J Nanomedicine (2014)

Magnetization curves for different SEONDEX after normalization to the volume fraction of the magnetic phase.Note: All data sets showed no hysteresis and no remanence.Abbreviations: SEONDEX, dextran-coated SPIONs; SPIONs, superparamagnetic iron oxide nanoparticles.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128796&req=5

f5-ijn-9-3659: Magnetization curves for different SEONDEX after normalization to the volume fraction of the magnetic phase.Note: All data sets showed no hysteresis and no remanence.Abbreviations: SEONDEX, dextran-coated SPIONs; SPIONs, superparamagnetic iron oxide nanoparticles.
Mentions: The magnetic properties of SEONDEX are also very important because after administration of the drug delivery vehicles into the body, they are positioned in the tumor tissue with the aid of an external magnetic field. The magnetization curves for SEONDEX were recorded by means of SQUID measurements, which are depicted in Figure 5. All samples show superparamagnetic behavior, with a saturation magnetization dependent on the dextran concentration during precipitation (Table 3). The sample with the amount of lowest dextran showed a saturation magnetization of 454±23 kA/m, whereas the sample with the highest content showed a value of 186±10 kA/m. The value for SEONDEX 2.0 is comparable with that of bulk magnetite, the saturation magnetization of which is 480 kA/m at room temperature.46 In general, the decrease can be explained with the results outlined above. The X-ray diffraction patterns show lesser crystallinity with increasing dextran content, which is why the saturation magnetization is reduced. The curves also showed no hysteresis or residual magnetization. This is very important because once the applied field is removed from the particles, the lack of residual magnetization reduces the probability of agglomeration, thereby avoiding uptake by phagocytes as well as the danger of thrombosis.12

Bottom Line: In this project, SPIONs with a dextran and cisplatin-bearing hyaluronic acid coating were successfully synthesized as a novel cisplatin drug delivery system.The resulting amide bond linkage was verified using Fourier transform infrared spectroscopy.In conclusion, combination of dextran-coated SPIONs with hyaluronic acid and cisplatin represents a promising approach for magnetic drug targeting in the treatment of cancer.

View Article: PubMed Central - PubMed

Affiliation: ENT Department, Section of Experimental Oncology and Nanomedicine (SEON), Else Kroener-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Germany.

ABSTRACT
A highly selective and efficient cancer therapy can be achieved using magnetically directed superparamagnetic iron oxide nanoparticles (SPIONs) bearing a sufficient amount of the therapeutic agent. In this project, SPIONs with a dextran and cisplatin-bearing hyaluronic acid coating were successfully synthesized as a novel cisplatin drug delivery system. Transmission electron microscopy images as well as X-ray diffraction analysis showed that the individual magnetite particles were around 4.5 nm in size and monocrystalline. The small crystallite sizes led to the superparamagnetic behavior of the particles, which was exemplified in their magnetization curves, acquired using superconducting quantum interference device measurements. Hyaluronic acid was bound to the initially dextran-coated SPIONs by esterification. The resulting amide bond linkage was verified using Fourier transform infrared spectroscopy. The additional polymer layer increased the vehicle size from 22 nm to 56 nm, with a hyaluronic acid to dextran to magnetite weight ratio of 51:29:20. A maximum payload of 330 μg cisplatin/mL nanoparticle suspension was achieved, thus the particle size was further increased to around 77 nm with a zeta potential of -45 mV. No signs of particle precipitation were observed over a period of at least 8 weeks. Analysis of drug-release kinetics using the dialysis tube method revealed that these were driven by inverse ligand substitution and diffusion through the polymer shell as well as enzymatic degradation of hyaluronic acid. The biological activity of the particles was investigated in a nonadherent Jurkat cell line using flow cytometry. Further, cell viability and proliferation was examined in an adherent PC-3 cell line using xCELLigence analysis. Both tests demonstrated that particles without cisplatin were biocompatible with these cells, whereas particles with the drug induced apoptosis in a dose-dependent manner, with secondary necrosis after prolonged incubation. In conclusion, combination of dextran-coated SPIONs with hyaluronic acid and cisplatin represents a promising approach for magnetic drug targeting in the treatment of cancer.

Show MeSH
Related in: MedlinePlus