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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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Size of the nanoparticles increased after application of the hyaluronic acid coating and the incorporation of the drug (A). Change in zeta potential of the colloid after functionalization, esterification, and incorporation of the drug (B).Abbreviations: SEONDEX, dextran-coated SPIONs; SPIONs, superparamagnetic iron oxide nanoparticles; CPt, cisplatin; HA, hyaluronic acid; SEONDEX-NH2, aminated SEONDEX.
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f7-ijn-9-3659: Size of the nanoparticles increased after application of the hyaluronic acid coating and the incorporation of the drug (A). Change in zeta potential of the colloid after functionalization, esterification, and incorporation of the drug (B).Abbreviations: SEONDEX, dextran-coated SPIONs; SPIONs, superparamagnetic iron oxide nanoparticles; CPt, cisplatin; HA, hyaluronic acid; SEONDEX-NH2, aminated SEONDEX.

Mentions: Prior to esterification, the amination of SEONDEX led to SEONDEX-NH2 with a size of 22±0.2 nm. The functionalization changed the zeta potential from −2.5±0.8 mV to 25.8±0.8 mV at pH 7.5 in an aqueous solution. Esterification with pure HA resulted in SEONDEX-HA with a size of 56.0±4.6 nm, as depicted in Figure 7A. Taking the iron concentration and the change in solid content into account, the particles consisted of 51% HA, 29% dextran, and 20% magnetite. Due to the anionic character of HA, the zeta potential was reversed to -33.9±0.7 mV in water at pH 7.5 (Figure 7B), which enabled electrostatic stabilization. SEONDEX-HA did not precipitate after weeks of storage. After incorporation of the drug, the particle size increased further to 76.7±5.6 nm and the zeta potential changed to −45.0±0.3 mV (in water at pH 7.5). The reason behind this increase was the formation of a polymer-metal complex between the carboxylic acid of HA and the platinum atom of cisplatin, which changed the folding and conformation of the polymer. The SEONDEX-HA*CPt were also stable in water. This approach was efficient in terms of drug encapsulation efficacy (43.2%±3%) and in terms of the total amount of incorporated drug (330±10 μg/mL).


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)

Size of the nanoparticles increased after application of the hyaluronic acid coating and the incorporation of the drug (A). Change in zeta potential of the colloid after functionalization, esterification, and incorporation of the drug (B).Abbreviations: SEONDEX, dextran-coated SPIONs; SPIONs, superparamagnetic iron oxide nanoparticles; CPt, cisplatin; HA, hyaluronic acid; SEONDEX-NH2, aminated SEONDEX.
© Copyright Policy
Related In: Results  -  Collection

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

f7-ijn-9-3659: Size of the nanoparticles increased after application of the hyaluronic acid coating and the incorporation of the drug (A). Change in zeta potential of the colloid after functionalization, esterification, and incorporation of the drug (B).Abbreviations: SEONDEX, dextran-coated SPIONs; SPIONs, superparamagnetic iron oxide nanoparticles; CPt, cisplatin; HA, hyaluronic acid; SEONDEX-NH2, aminated SEONDEX.
Mentions: Prior to esterification, the amination of SEONDEX led to SEONDEX-NH2 with a size of 22±0.2 nm. The functionalization changed the zeta potential from −2.5±0.8 mV to 25.8±0.8 mV at pH 7.5 in an aqueous solution. Esterification with pure HA resulted in SEONDEX-HA with a size of 56.0±4.6 nm, as depicted in Figure 7A. Taking the iron concentration and the change in solid content into account, the particles consisted of 51% HA, 29% dextran, and 20% magnetite. Due to the anionic character of HA, the zeta potential was reversed to -33.9±0.7 mV in water at pH 7.5 (Figure 7B), which enabled electrostatic stabilization. SEONDEX-HA did not precipitate after weeks of storage. After incorporation of the drug, the particle size increased further to 76.7±5.6 nm and the zeta potential changed to −45.0±0.3 mV (in water at pH 7.5). The reason behind this increase was the formation of a polymer-metal complex between the carboxylic acid of HA and the platinum atom of cisplatin, which changed the folding and conformation of the polymer. The SEONDEX-HA*CPt were also stable in water. This approach was efficient in terms of drug encapsulation efficacy (43.2%±3%) and in terms of the total amount of incorporated drug (330±10 μg/mL).

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