title: Development and characterization of magnetic iron oxide nanoparticles with a cisplatin-bearing polymer coating for targeted drug delivery.
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.
authors.affiliation: ENT Department, Section of Experimental Oncology and Nanomedicine (SEON), Else Kroener-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Unterweger
authors.affiliation: ENT Department, Section of Experimental Oncology and Nanomedicine (SEON), Else Kroener-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Tietze
authors.affiliation: ENT Department, Section of Experimental Oncology and Nanomedicine (SEON), Else Kroener-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Janko
authors.affiliation: ENT Department, Section of Experimental Oncology and Nanomedicine (SEON), Else Kroener-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Zaloga
authors.affiliation: ENT Department, Section of Experimental Oncology and Nanomedicine (SEON), Else Kroener-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lyer
authors.affiliation: ENT Department, Section of Experimental Oncology and Nanomedicine (SEON), Else Kroener-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Dürr
authors.affiliation: Chair of Chemical Engineering I (Reaction Engineering), University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Taccardi
authors.affiliation: Institute of Biomaterials, Department of Materials Science and Engineering, University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Ourania-Menti
authors.initials: OM
authors.lastname: Goudouri
authors.affiliation: Institute of Biomaterials, Department of Materials Science and Engineering, University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hoppe
authors.affiliation: Physikalisch-Technische Bundesanstalt, Berlin, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Eberbeck
authors.affiliation: Institute of Polymer Materials, Department of Materials Science and Engineering, University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Dirk W
authors.initials: DW
authors.lastname: Schubert
authors.affiliation: Institute of Biomaterials, Department of Materials Science and Engineering, University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Aldo R
authors.initials: AR
authors.lastname: Boccaccini
authors.affiliation: ENT Department, Section of Experimental Oncology and Nanomedicine (SEON), Else Kroener-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Alexiou
mesh_terms: D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D003911:Dextrans / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D019169:Jurkat Cells; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D010316:Particle Size
chemical_list: D003911:Dextrans; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D006820:Hyaluronic Acid; D002945:Cisplatin
keywords: dextran; hyaluronic acid; magnetic drug targeting; superparamagnetic iron oxide nanoparticles